Heart Failure With Preserved Ejection Fraction in the Young.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF), traditionally considered a disease of the elderly, may also affect younger patients. However, little is known about HFpEF in the young. METHODS: We prospectively enrolled 1203 patients with HFpEF (left ventricular ejection fraction ≥50%) from 11 Asian regions. We grouped HFpEF patients into very young (<55 years of age; n=157), young (55-64 years of age; n=284), older (65-74 years of age; n=355), and elderly (≥75 years of age; n=407) and compared clinical and echocardiographic characteristics, quality of life, and outcomes across age groups and between very young individuals with HFpEF and age- and sex-matched control subjects without heart failure. RESULTS: Thirty-seven percent of our HFpEF population was <65 years of age. Younger age was associated with male preponderance and a higher prevalence of obesity (body mass index ≥30 kg/m2; 36% in very young HFpEF versus 16% in elderly) together with less renal impairment, atrial fibrillation, and hypertension (all P<0.001). Left ventricular filling pressures and prevalence of left ventricular hypertrophy were similar in very young and elderly HFpEF. Quality of life was better and death and heart failure hospitalization at 1 year occurred less frequently ( P<0.001) in the very young (7%) compared with elderly (21%) HFpEF. Compared with control subjects, very young HFpEF had a 3-fold higher death rate and twice the prevalence of hypertrophy. CONCLUSIONS: Young and very young patients with HFpEF display similar adverse cardiac remodeling compared with their older counterparts and very poor outcomes compared with control subjects without heart failure. Obesity may be a major driver of HFpEF in a high proportion of HFpEF in the young and very young.

Association of obesity with heart failure outcomes in 11 Asian regions: A cohort study.

BACKGROUND: Asians are predisposed to a lean heart failure (HF) phenotype. Data on the 'obesity paradox', reported in Western populations, are scarce in Asia and have only utilised the traditional classification of body mass index (BMI). We aimed to investigate the association between obesity (defined by BMI and abdominal measures) and HF outcomes in Asia. METHODS AND FINDINGS: Utilising the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry (11 Asian regions including Taiwan, Hong Kong, China, India, Malaysia, Thailand, Singapore, Indonesia, Philippines, Japan, and Korea; 46 centres with enrolment between 1 October 2012 and 6 October 2016), we prospectively examined 5,964 patients with symptomatic HF (mean age 61.3 ± 13.3 years, 26% women, mean BMI 25.3 ± 5.3 kg/m2, 16% with HF with preserved ejection fraction [HFpEF; ejection fraction ≥ 50%]), among whom 2,051 also had waist-to-height ratio (WHtR) measurements (mean age 60.8 ± 12.9 years, 24% women, mean BMI 25.0 ± 5.2 kg/m2, 7% HFpEF). Patients were categorised by BMI quartiles or WHtR quartiles or 4 combined groups of BMI (low, <24.5 kg/m2 [lean], or high, ≥24.5 kg/m2 [obese]) and WHtR (low, <0.55 [thin], or high, ≥0.55 [fat]). Cox proportional hazards models were used to examine a 1-year composite outcome (HF hospitalisation or mortality). Across BMI quartiles, higher BMI was associated with lower risk of the composite outcome (ptrend < 0.001). Contrastingly, higher WHtR was associated with higher risk of the composite outcome. Individuals in the lean-fat group, with low BMI and high WHtR (13.9%), were more likely to be women (35.4%) and to be from low-income countries (47.7%) (predominantly in South/Southeast Asia), and had higher prevalence of diabetes (46%), worse quality of life scores (63.3 ± 24.2), and a higher rate of the composite outcome (51/232; 22%), compared to the other groups (p < 0.05 for all). Following multivariable adjustment, the lean-fat group had higher adjusted risk of the composite outcome (hazard ratio 1.93, 95% CI 1.17-3.18, p = 0.01), compared to the obese-thin group, with high BMI and low WHtR. Results were consistent across both HF subtypes (HFpEF and HF with reduced ejection fraction [HFrEF]; pinteraction = 0.355). Selection bias and residual confounding are potential limitations of such multinational observational registries. CONCLUSIONS: In this cohort of Asian patients with HF, the 'obesity paradox' is observed only when defined using BMI, with WHtR showing the opposite association with the composite outcome. Lean-fat patients, with high WHtR and low BMI, have the worst outcomes. A direct correlation between high WHtR and the composite outcome is apparent in both HFpEF and HFrEF. TRIAL REGISTRATION: Asian Sudden Cardiac Death in HF (ASIAN-HF) Registry ClinicalTrials.gov Identifier: NCT01633398.

Correction: Multimorbidity in patients with heart failure from 11 Asian regions: A prospective cohort study using the ASIAN-HF registry.

[This corrects the article DOI: 10.1371/journal.pmed.1002541.].

Multimorbidity in patients with heart failure from 11 Asian regions: A prospective cohort study using the ASIAN-HF registry.

BACKGROUND: Comorbidities are common in patients with heart failure (HF) and complicate treatment and outcomes. We identified patterns of multimorbidity in Asian patients with HF and their association with patients' quality of life (QoL) and health outcomes. METHODS AND FINDINGS: We used data on 6,480 patients with chronic HF (1,204 with preserved ejection fraction) enrolled between 1 October 2012 and 6 October 2016 in the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry. The ASIAN-HF registry is a prospective cohort study, with patients prospectively enrolled from in- and outpatient clinics from 11 Asian regions (Hong Kong, Taiwan, China, Japan, Korea, India, Malaysia, Thailand, Singapore, Indonesia, and Philippines). Latent class analysis was used to identify patterns of multimorbidity. The primary outcome was defined as a composite of all-cause mortality or HF hospitalization within 1 year. To assess differences in QoL, we used the Kansas City Cardiomyopathy Questionnaire. We identified 5 distinct multimorbidity groups: elderly/atrial fibrillation (AF) (N = 1,048; oldest, more AF), metabolic (N = 1,129; obesity, diabetes, hypertension), young (N = 1,759; youngest, low comorbidity rates, non-ischemic etiology), ischemic (N = 1,261; ischemic etiology), and lean diabetic (N = 1,283; diabetic, hypertensive, low prevalence of obesity, high prevalence of chronic kidney disease). Patients in the lean diabetic group had the worst QoL, more severe signs and symptoms of HF, and the highest rate of the primary combined outcome within 1 year (29% versus 11% in the young group) (p for all <0.001). Adjusting for confounders (demographics, New York Heart Association class, and medication) the lean diabetic (hazard ratio [HR] 1.79, 95% CI 1.46-2.22), elderly/AF (HR 1.57, 95% CI 1.26-1.96), ischemic (HR 1.51, 95% CI 1.22-1.88), and metabolic (HR 1.28, 95% CI 1.02-1.60) groups had higher rates of the primary combined outcome compared to the young group. Potential limitations include site selection and participation bias. CONCLUSIONS: Among Asian patients with HF, comorbidities naturally clustered in 5 distinct patterns, each differentially impacting patients' QoL and health outcomes. These data underscore the importance of studying multimorbidity in HF and the need for more comprehensive approaches in phenotyping patients with HF and multimorbidity. TRIAL REGISTRATION: ClinicalTrials.gov NCT01633398.

High-dose intravenous iron reduces myocardial infarction in patients on haemodialysis.

AIMS: To investigate the effect of high-dose iron vs. low-dose intravenous (IV) iron on myocardial infarction (MI) in patients on maintenance haemodialysis. METHODS AND RESULTS: This was a pre-specified analysis of secondary endpoints of the Proactive IV Iron Therapy in Hemodialysis Patients trial (PIVOTAL) randomized, controlled clinical trial. Adults who had started haemodialysis within the previous year, who had a ferritin concentration <400 µg per litre and a transferrin saturation <30% were randomized to high-dose or low-dose IV iron. The main outcome measure for this analysis was fatal or non-fatal MI. Over a median of 2.1 years of follow-up, 8.4% experienced a MI. Rates of type 1 MIs (3.2/100 patient-years) were 2.5 times higher than type 2 MIs (1.3/100 patient-years). Non-ST-elevation MIs (3.3/100 patient-years) were 6 times more common than ST-elevation MIs (0.5/100 patient-years). Mortality was high after non-fatal MI (1- and 2-year mortality of 40% and 60%, respectively). In time-to-first event analyses, proactive high-dose IV iron reduced the composite endpoint of non-fatal and fatal MI [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.52-0.93, P = 0.01] and non-fatal MI (HR 0.69, 95% CI 0.51-0.93; P = 0.01) when compared with reactive low-dose IV iron. There was less effect of high-dose IV iron on recurrent MI events than on the time-to-first event analysis. CONCLUSION: In total, 8.4% of patients on maintenance haemodialysis had an MI over 2 years. High-dose compared to low-dose IV iron reduced MI in patients receiving haemodialysis. EUDRACT REGISTRATION NUMBER: 2013-002267-25.

Intensive glycemic control has no impact on the risk of heart failure in type 2 diabetic patients: evidence from a 37,229 patient meta-analysis.

BACKGROUND: More intensive glycemic control reduces the risk of microvascular disease in patients with diabetes mellitus but has not been proven to reduce the risk of macrovascular events such as myocardial infarction and stroke. Poorer glycemic control, as indicated by glycated hemoglobin level concentration, is associated with an increased risk of heart failure (HF), but it is not known whether improved glycemic control reduces this risk. We conducted a meta-analysis of randomized controlled trials comparing strategies of more versus less intensive glucose-lowering that reported HF events. METHODS: Two investigators independently searched PubMed, the Cochrane CENTRAL register of controlled trials, metaRegister, pre-MEDLINE, and CINAHL from January 1970 to October 2010 for prospective controlled randomized trials comparing a more intensive glucose-lowering regimen to a standard regimen. The outcome of interest was HF-related events (both fatal and nonfatal). Odds ratios (ORs) were calculated from published data from relevant trials and pooled with a random-effects meta-analysis. RESULTS: A total of 37,229 patients from 8 randomized trials were included in the analysis. Follow-up ranged from 2.3 to 10.1 years, and the overall number of HF-related events was 1469 (55% in the intensive treatment arm). The mean difference in glycated hemoglobin level between patients given standard treatment and those allocated to a more intensive regimen was 0.9%. Overall, the risk of HF-related events did not differ significantly between intensive glycemic control and standard treatment (OR 1.20, 95% CI 0.96-1.48), but the effect estimate was highly heterogeneous (I(2) = 69%). At subgroup analysis, intensive glycemic control achieved with high thiazolidinediones use significantly increased HF risk (OR 1.33, 95% CI 1.02-1.72). CONCLUSIONS: More intensive glycemic control in patients with type 2 diabetes mellitus did not reduce the occurrence of HF events. Furthermore, intensive glycemic control with thiazolidinediones increased the risk of HF. These findings question a direct mechanistic link between hyperglycemia and HF.

Heart Failure Hospitalization in Adults Receiving Hemodialysis and the Effect of Intravenous Iron Therapy.

OBJECTIVES: This study sought to examine the effect of intravenous iron on heart failure events in hemodialysis patients. BACKGROUND: Heart failure is a common and deadly complication in patients receiving hemodialysis and is difficult to diagnose and treat. METHODS: The study analyzed heart failure events in the PIVOTAL (Proactive IV Iron Therapy in Hemodialysis Patients) trial, which compared intravenous iron administered proactively in a high-dose regimen with a low-dose regimen administered reactively. Heart failure hospitalization was an adjudicated outcome, a component of the primary composite outcome, and a prespecified secondary endpoint in the trial. RESULTS: Overall, 2,141 participants were followed for a median of 2.1 years. A first fatal or nonfatal heart failure event occurred in 51 (4.7%) of 1,093 patients in the high-dose iron group and in 70 (6.7%) of 1,048 patients in the low-dose group (HR: 0.66; 95% CI: 0.46-0.94; P = 0.023). There was a total of 63 heart failure events (including first and recurrent events) in the high-dose iron group and 98 in the low-dose group, giving a rate ratio of 0.59 (95% CI: 0.40-0.87; P = 0.0084). Most patients presented with pulmonary edema and were mainly treated by mechanical removal of fluid. History of heart failure and diabetes were independent predictors of a heart failure event. CONCLUSIONS: Compared with a lower-dose regimen, high-dose intravenous iron decreased the occurrence of first and recurrent heart failure events in patients undergoing hemodialysis, with large relative and absolute risk reductions. (UK Multicentre Open-label Randomised Controlled Trial Of IV Iron Therapy In Incident Haemodialysis Patients; 2013-002267-25).

Electroanatomic Ratios and Mortality in Patients With Heart Failure: Insights from the ASIAN-HF Registry.

Background QRS duration (QRSd) is a marker of electrical remodeling in heart failure. Anthropometrics and left ventricular size may influence QRSd and, in turn, may influence the association between QRSd and heart failure outcomes. Methods and Results Using the prospective, multicenter, multinational ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) registry, this study evaluated whether electroanatomic ratios (QRSd indexed for height or left ventricular end-diastole volume) are associated with 1-year mortality in individuals with heart failure with reduced ejection fraction. The study included 4899 individuals (aged 60±19 years, 78% male, mean left ventricular ejection fraction: 27.3±7.1%). In the overall cohort, QRSd was not associated with all-cause mortality (hazard ratio [HR], 1.003; 95% CI, 0.999-1.006, P=0.142) or sudden cardiac death (HR, 1.006; 95% CI, 1.000-1.013, P=0.059). QRS/height was associated with all-cause mortality (HR, 1.165; 95% CI, 1.046-1.296, P=0.005 with interaction by sex pinteraction=0.020) and sudden cardiac death (HR, 1.270; 95% CI, 1.021-1.580, P=0.032). QRS/left ventricular end-diastole volume was associated with all-cause mortality (HR, 1.22; 95% CI, 1.05-1.43, P=0.011) and sudden cardiac death (HR, 1.461; 95% CI, 1.090-1.957, P=0.011) in patients with nonischemic cardiomyopathy but not in patients with ischemic cardiomyopathy (all-cause mortality: HR, 0.94; 95% CI, 0.79-1.11, P=0.467; sudden cardiac death: HR, 0.734; 95% CI, 0.477-1.132, P=0.162). Conclusions Electroanatomic ratios of QRSd indexed for body size or left ventricular size are associated with mortality in individuals with heart failure with reduced ejection fraction. In particular, increased QRS/height may be a marker of high risk in individuals with heart failure with reduced ejection fraction, and QRS/left ventricular end-diastole volume may further risk stratify individuals with nonischemic heart failure with reduced ejection fraction. Registration URL: https://Clinicaltrials.gov. Unique identifier: NCT01633398.

Effectiveness of telemonitoring-enhanced support over structured telephone support in reducing heart failure-related healthcare utilization in a multi-ethnic Asian setting.

AIMS: Our study aimed to compare the effectiveness of telemonitoring over structured telephone support in reducing heart failure-related healthcare utilization. METHODS: This was a non-randomised controlled study comparing 150 recently discharged heart failure patients enrolled into telemonitoring and 55 patients who only received structured telephone support after rejecting telemonitoring. Patient activation, knowledge and self-management levels were measured at baseline and the one year upon programme completion using the Patient Activation Measure, the Dutch Heart Failure Knowledge Scale and the Self-Care of Heart Failure Index respectively. Differences in heart failure-related and all-cause hospitalization rates, total bed days and mortality rates at 180 days and at one year, knowledge and self-management scores and total cost of care between groups at one year were analysed. RESULTS: Average age of telemonitoring was 57.9 years and 63.9 years for structured telephone support. Significant difference in adjusted 180-day all-cause bed days (telemonitoring: five days versus structured telephone support: 9.8 days), heart failure-related bed days (telemonitoring: 1.2 days versus structured telephone support: six days) and adjusted one-year heart failure-related bed days (telemonitoring: 2.2 days versus structured telephone support: 6.6 days) were observed. Telemonitoring was associated with reduced all-cause one-year mortality (hazard ratio 0.32, p = 0.02). Estimated mean maintenance and confidence scores were significantly higher in the telemonitoring group at one year. No differences in all-cause and HF-related readmission rates and knowledge levels were observed. The one-year total cost of care was predicted to be Singapore dollars (SG$) 2774.4 lower (p = 0.07) in telemonitoring. CONCLUSION: In conclusion, telemonitoring was associated with lower all-cause and heart failure-related total bed days at 180 days, lower heart failure-related total bed days and total cost of care at one year as compared with structured telephone support.

Regional Variation of Mortality in Heart Failure With Reduced and Preserved Ejection Fraction Across Asia: Outcomes in the ASIAN-HF Registry.

Background Data comparing outcomes in heart failure (HF) across Asia are limited. We examined regional variation in mortality among patients with HF enrolled in the ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) registry with separate analyses for those with reduced ejection fraction (EF; <40%) versus preserved EF (≥50%). Methods and Results The ASIAN-HF registry is a prospective longitudinal study. Participants with symptomatic HF were recruited from 46 secondary care centers in 3 Asian regions: South Asia (India), Southeast Asia (Thailand, Malaysia, Philippines, Indonesia, Singapore), and Northeast Asia (South Korea, Japan, Taiwan, Hong Kong, China). Overall, 6480 patients aged >18 years with symptomatic HF were recruited (mean age: 61.6±13.3 years; 27% women; 81% with HF and reduced rEF). The primary outcome was 1-year all-cause mortality. Striking regional variations in baseline characteristics and outcomes were observed. Regardless of HF type, Southeast Asians had the highest burden of comorbidities, particularly diabetes mellitus and chronic kidney disease, despite being younger than Northeast Asian participants. One-year, crude, all-cause mortality for the whole population was 9.6%, higher in patients with HF and reduced EF (10.6%) than in those with HF and preserved EF (5.4%). One-year, all-cause mortality was significantly higher in Southeast Asian patients (13.0%), compared with South Asian (7.5%) and Northeast Asian patients (7.4%; P<0.001). Well-known predictors of death accounted for only 44.2% of the variation in risk of mortality. Conclusions This first multinational prospective study shows that the outcomes in Asian patients with both HF and reduced or preserved EF are poor overall and worst in Southeast Asian patients. Region-specific risk factors and gaps in guideline-directed therapy should be addressed to potentially improve outcomes. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01633398.

Ethnic differences in atrial fibrillation among patients with heart failure in Asia.

AIMS: We aimed to characterize ethnic differences in prevalence, clinical correlates, and outcomes of atrial fibrillation (AF) in heart failure (HF) with preserved and reduced ejection fraction (HFpEF and HFrEF) across Asia. METHODS AND RESULTS: Among 5504 patients with HF prospectively recruited across 11 Asian regions using identical protocols in the Asian Sudden Cardiac Death in Heart Failure study (mean age 61 ± 13 years, 27% women, 83% HFrEF), 1383 (25%) had AF defined as a history of AF and/or AF/flutter on baseline electrocardiogram. Clinical correlates of AF were similar across ethnicities and included older age, prior stroke, higher NT-proBNP, and larger left atria. Diabetes was associated with lower odds of AF in HFrEF [adjusted odds ratio (AOR) 0.79, 95% CI 0.66-0.95] and HFpEF (AOR 0.58, 95% CI 0.39-0.84) regardless of ethnicity. Compared with Chinese ethnicity, Japanese/Koreans had higher odds of AF in HFrEF (AOR 1.76, 95% CI 1.40-2.21), while Indians had lower odds in HFrEF (AOR 0.18, 95% CI 0.13-0.24) and HFpEF (AOR 0.28, 95% CI 0.16-0.49) even after adjusting for clinical covariates. Interaction between ethnicity and region was observed among Indians, with Southeast Asian Indians having higher odds of AF (AOR 3.01, 95% CI 1.60-5.67) compared with South Asian Indians. AF was associated with poorer quality of life and increased risk of 1 year all-cause mortality or HF hospitalisation (adjusted hazard ratio 1.39, 95% CI 1.18-1.63) regardless of ethnicity. CONCLUSIONS: Among patients with HF across Asia, clinical correlates and adverse outcomes associated with AF are similar across ethnicities; however, there are striking ethnic variations in the prevalence of AF that are not accounted for by known risk factors.

Bisoprolol in patients with heart failure and moderate to severe chronic obstructive pulmonary disease: a randomized controlled trial.

AIMS: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) frequently coexist. No study has prospectively examined the effects of beta-blockade in those with both conditions. METHODS AND RESULTS: We randomized 27 patients with HF and coexistent moderate or severe COPD to receive bisoprolol or placebo, titrated to maximum tolerated dose over 4 months. The primary outcome was forced expiratory volume in 1 s (FEV(1)). The study is registered with ClinicalTrials.gov, number: NCT00702156. Patients were elderly and predominantly male. Cardiovascular comorbidity, smoking history, and pulmonary function were similar in each group (mean FEV(1) 1.37 vs. 1.26 L, P = 0.52). A reduction in FEV(1) occurred after 4 months following treatment with bisoprolol compared with placebo (-70 vs. +120 mL, P = 0.01). Reversibility following inhaled beta(2)-agonist and static lung volumes were not impaired by bisoprolol. All measures of health status exhibited a consistent non-significant improvement, including the Short Form 36 physical and mental component scores (2.6 vs. 0.5 and 0.8 vs. -0.3, respectively), Minnesota Living with Heart Failure Questionnaire (-2.5 vs. 3.5) and Chronic Respiratory Questionnaire (0.07 vs. -0.24). The mean number of COPD exacerbations was similar in the bisoprolol and placebo groups (0.50 and 0.31, respectively, P = 0.44). CONCLUSION: Initiation of bisoprolol in patients with HF and concomitant moderate or severe COPD resulted in a reduction in FEV(1). However, symptoms and quality of life were not impaired.

Pharmacologic management of patients with both heart failure and diabetes.

Diabetes and heart failure often occur together in patients, with each condition influencing the treatment of the other. Each disease has its own well-documented impact on prognosis, but when they are present in the same patient, the risk of morbidity and mortality increases substantially. Some therapies used in the treatment of diabetes are contraindicated in patients with heart failure, and some therapies for treating heart failure are often mistakenly believed to be contraindicated in patients with diabetes. This article aims to clarify the evidence behind treating these conditions simultaneously and dispel the myths surrounding the pharmacologic management of diabetes in heart failure and vice versa.

Diabetes, left ventricular systolic dysfunction, and chronic heart failure.

Chronic heart failure (HF) and diabetes mellitus (DM) commonly coexist. Each condition increases the likelihood of developing the other, and when they occur together in the same patient the risk of morbidity and mortality increases markedly. We discuss the epidemiological overlap and consider the complex patho-physiological pathways linking the two diseases. The treatment of each condition is made more problematic by the presence of the other. We review the evidence-based treatment strategies and discuss the common problems faced by physicians when treating patients with both conditions. This article forms a comprehensive overview of a fascinating intersection between two common diseases.

Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme.

AIMS: To determine whether the risk of adverse cardiovascular (CV) outcomes associated with diabetes differs in patients with low and preserved ejection fraction (EF) heart failure (HF). METHODS AND RESULTS: We analysed outcomes in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme which randomized 7599 patients with symptomatic HF and a broad range of EF. The prevalence of diabetes was 28.3% in patients with preserved EF (>40%) and 28.5% in those with low EF (

Association of Diabetes Mellitus on Cardiac Remodeling, Quality of Life, and Clinical Outcomes in Heart Failure With Reduced and Preserved Ejection Fraction.

Background Diabetes mellitus frequently coexists with heart failure (HF), but few studies have compared the associations between diabetes mellitus and cardiac remodeling, quality of life, and clinical outcomes, according to HF phenotype. Methods and Results We compared echocardiographic parameters, quality of life (assessed by the Kansas City Cardiomyopathy Questionnaire), and outcomes (1-year all-cause mortality, cardiovascular mortality, and HF hospitalization) between HF patients with and without type 2 diabetes mellitus in the prospective ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) Registry, as well as community-based controls without HF. Adjusted Cox proportional hazards models were used to assess the association of diabetes mellitus with clinical outcomes. Among 5028 patients with HF and reduced ejection fraction (HFrEF; EF <40%) and 1139 patients with HF and preserved EF (HFpEF; EF ≥50%), the prevalences of type 2 diabetes mellitus were 40.2% and 45.0%, respectively (P=0.003). In both HFrEF and HFpEF cohorts, diabetes mellitus (versus no diabetes mellitus) was associated with smaller indexed left ventricular diastolic volumes and higher mitral E/e' ratio. There was a predominance of eccentric hypertrophy in HFrEF and concentric hypertrophy in HFpEF. Patients with diabetes mellitus had lower Kansas City Cardiomyopathy Questionnaire scores in both HFpEF and HFrEF, with more prominent differences in HFpEF (Pinteraction<0.05). In both HFpEF and HFrEF, patients with diabetes mellitus had more HF rehospitalizations (adjusted hazard ratio, 1.27; 95% CI, 1.05-1.54; P=0.014) and higher 1-year rates of the composite of all-cause mortality/HF hospitalization (adjusted hazard ratio, 1.22; 95% CI, 1.05-1.41; P=0.011), with no differences between HF phenotypes (Pinteraction>0.05). Conclusions In HFpEF and HFrEF, type 2 diabetes mellitus is associated with smaller left ventricular volumes, higher mitral E/e' ratio, poorer quality of life, and worse outcomes, with several differences noted between HF phenotypes. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01633398.

Defining a 'frequent admitter' phenotype among patients with repeat heart failure admissions.

AIMS: We aimed to identify a 'frequent admitter' phenotype among patients admitted for acute decompensated heart failure (HF). METHODS AND RESULTS: We studied 10 363 patients in a population-based prospective HF registry (2008-2012), segregated into clusters based on their 3-year HF readmission frequency trajectories. Using receiver-operating characteristic analysis, we identified the index year readmission frequency threshold that most accurately predicts HF admission frequency clusters. Two clusters of HF patients were identified: a high frequency cluster (90.9%, mean 2.35 ± 3.68 admissions/year) and a low frequency cluster (9.1%, mean 0.50 ± 0.81 admission/year). An index year threshold of two admissions was optimal for distinguishing between clusters. Based on this threshold, 'frequent admitters', defined as patients with ≥ 2 HF admissions in the index year (n = 2587), were of younger age (68 ± 13 vs 69 ± 13 years), more often male (58% vs. 54%), smokers (38.4% vs. 34.4%) and had lower left ventricular ejection fraction (37 ± 17 vs. 41 ± 17%) compared to 'non-frequent admitters' (< 2 HF admissions in the index year; n = 7776) (all P < 0.001). Despite similar rates of advanced care utilization, frequent admitters had longer length of stay (median 4.3 vs. 4.0 days), higher annual inpatient costs (€ 7015 vs. € 2967) and higher all-cause mortality at 3 years compared to the non-frequent admitters (adjusted odds ratio 2.33, 95% confidence interval 2.11-2.58; P < 0.001). CONCLUSION: 'Frequent admitters' have distinct clinical characteristics and worse outcomes compared to non-frequent admitters. This study may provide a means of anticipating the HF readmission burden and thereby aid in healthcare resource distribution relative to the HF admission frequency phenotype.

Impact of diabetes and sex in heart failure with reduced ejection fraction patients from the ASIAN-HF registry.

AIMS: To examine sex differences in clinical characteristics, echocardiographic features, quality of life and 1-year death or heart failure (HF) hospitalization outcomes in patients with/without diabetes mellitus (DM). METHODS AND RESULTS: Utilizing the Asian Sudden Cardiac Death in HF (ASIAN-HF) registry, 5255 patients (mean age 59.6 ± 13.1, 78% men) with symptomatic HF with reduced ejection fraction (HFrEF) were stratified by DM status to address the research aims. Despite similar prevalence of DM between Asian men (43%) and women (42%), the odds of DM increased at lower body mass index in women vs. men (≥ 23 vs. ≥ 27.5 kg/m2 , Pinteraction = 0.014). DM was more strongly related to chronic kidney disease in women vs. men [adjusted odds ratio (OR) 1.85, 95% confidence interval (CI) 1.33-2.57 vs. OR 1.32, 95% CI 1.11-1.56, Pinteraction = 0.009]. Sex also modified the relationship between DM and left ventricular geometry (Pinteraction = 0.003), whereby DM was associated with a more concentric left ventricular geometry in women than men. Women had lower quality of life than men (P < 0.001), in both DM and non-DM groups. DM was associated with worse composite outcomes at 1 year in women vs. men [hazard ratio (HR) 1.79, 95% CI 1.24-2.60 vs. HR 1.32, 95% CI 1.12-1.56; Pinteraction = 0.005). CONCLUSIONS: Asian women with HFrEF were more likely to have DM despite a lean body mass index, a greater burden of chronic kidney disease and more concentric left ventricular geometry, compared to men. Furthermore, DM confers worse quality of life, irrespective of sex, and a greater risk of adverse outcomes in women than men. These data underscore the need for sex-specific approaches to diabetes in patients with HF.