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Aim: To investigate the interplay of incident chronic kidney disease (CKD) and/or heart failure (HF) and their associations with prognosis in a large, population-based cohort with type 2 diabetes (T2DM).Methods: Patients aged ≥18 years with new-onset T2DM, without renal disease or HF at baseline, were identified from the territory-wide Clinical Data Analysis Reporting System between 2000 and 2015. Patients were followed up until December 31, 2020 for incident CKD and/or HF and all-cause mortality.Results: Among 102 488 patients (median age 66 years, 45.7% women, median follow-up 7.5 years), new-onset CKD occurred in 14 798 patients (14.4%), in whom 21.7% had HF. In contrast, among 9258 patients (9.0%) with new-onset HF, 34.6% had CKD. The median time from baseline to incident CKD or HF (4.4 vs. 4.1 years) did not differ. However, the median (interquartile range) time until incident HF after CKD diagnosis was 1.7 (0.5-3.6) years and was 1.2 (0.2-3.4) years for incident CKD after HF diagnosis (P < 0.001). The crude incidence of CKD was higher than that of HF: 17.6 (95% confidence interval [CI] 17.3-17.9) vs. 10.6 (95% CI 10.4-10.9)/1000 person-years, respectively, but incident HF was associated with a higher adjusted-mortality than incident CKD. The presence of either condition (vs. CKD/HF-free status) was associated with a three-fold hazard of death, whereas concomitant HF and CKD conferred a six to seven-fold adjusted hazard of mortality.Conclusion: Cardiorenal complications are common and are associated with high mortality risk among patients with new-onset T2DM. Close surveillance of these dual complications is crucial to reduce the burden of disease.

Background: We aimed to assess if discordance between patient-reported Kansas City Cardiomyopathy Questionnaire (KCCQ)-overall summary (os) score and physician-assessed New York Heart Association (NYHA) class is common among patients with heart failure (HF) with reduced or preserved ejection fraction, and determine its association with outcomes. Methods: A total of 4818 patients with HF were classified according to KCCQ-os score (range 0–100, dichotomized by median value 71.9 into high [good] versus low [bad]) and NYHA class (I/II [good] or III/IV [bad]) as concordant good (low NYHA class, high KCCQ-os score), concordant bad (high NYHA class, low KCCQ-os score), discordant worse NYHA class (high NYHA class, high KCCQ-os score), and discordant worse KCCQ-os score (low NYHA class, low-KCCQ-os score). The composite of HF hospitalization or death at 1 year was compared across groups. Results: There were 2070 (43.0%) concordant good, 1099 (22.8%) concordant bad, 331 (6.9%) discordant worse NYHA class, and 1318 (27.4%) discordant worse KCCQ-os score patients. Compared with concordant good, adverse outcomes were the highest in concordant bad (HR, 2.7 [95% CI, 2.2–3.5]) followed by discordant worse KCCQ-os score (HR, 1.8 [95% CI, 1.4–2.2]) and discordant worse NYHA class (HR, 1.5 [95% CI, 1.0–2.3]); with no modification by HF phenotype (preserved versus reduced ejection fraction, P interaction =0.52). At 6 months, 1403 (48%) experienced clinically significant improvement in KCCQ-os score (≥5 points increase over 6 months). Patients with improved KCCQ-os at 6 months (HR, 0.65 [95% CI, 0.47–0.92]) had better outcomes and the association was not modified by HF phenotype ( P interaction =0.40). Conclusions: One-third of patients with HF had discordance between patient-reported and clinician-assessed health status, largely attributable to worse patient-reported outcomes. Such discordance, particularly in those with discordantly worse KCCQ, should alert physicians to an increased risk of HF hospitalization and death, and prompt further assessment for potential drivers of worse patient-reported outcomes relative to physicians’ assessment.

Aims In patients with heart failure (HF), hospitalization rates are increasing, particularly for non-HF causes and over half may be avoidable. Self-monitoring of symptoms plays a key part in the early identification of deterioration. Our objective was to develop expert consensus for a core outcome set (COS) of symptoms to be monitored by patients, using validated single-item patient-reported outcome measures (PROMs), focused on the key priority of reducing admissions in HF. Methods and results A rigorous COS development process incorporating systematic review, modified e-Delphi and nominal group technique (NGT) methods. Participants included 24 HF patients, 4 carers, 29 HF nurses, and 9 doctors. In three Delphi and NGT rounds, participants rated potential outcomes on their importance before a HF or a non-HF admission using a 5-point Likert scale. Opinion change between rounds was assessed and a two-thirds threshold was used for outcome selection. Item generation using systematic review identified 100 validated single-item PROMs covering 34 symptoms or signs, relevant to admission for people with HF. De-duplication and formal consensus processes, resulted in a COS comprising eight symptoms and signs; shortness of breath, arm or leg swelling, abdomen bloating, palpitations, weight gain, chest pain, anxiety, and overall health. In the NGT, a numerical rating scale was selected as the optimal approach to symptom monitoring. Conclusion Recognition of a range of HF-specific and general symptoms, alongside comorbidities, is an important consideration for admission prevention. Further work is needed to validate and integrate the COS in routine care with the aim of facilitating faster identification of clinical deterioration.

Different associations between epicardial adipose tissue (EAT) and cardiac function have been suggested in patients with heart failure with preserved (HFpEF) versus reduced and mildly reduced ejection fraction (HFrEF/HFmrEF). However, few studies have directly compared the association between EAT and left atrial (LA) and left ventricular (LV) function in patients with HFpEF and HFrEF/HFmrEF.We studied EAT thickness using transthoracic echocardiography in a multicentre cohort of 149 community-dwelling controls without heart failure, 99 patients with HFpEF, and 366 patients with HFrEF/HFmrEF. EAT thickness was averaged from parasternal long-axis and short-axis views, respectively, and off-line speckle tracking analysis was performed to quantify LA and LV function. Data were validated in an independent cohort of 626 controls, 243 patients with HFpEF, and 180 patients with HFrEF/HFmrEF. For LV function, LV global longitudinal strain (GLS) was measured in both derivation and validation cohorts. For LA function, LAGLS at reservoir, contractile and conduit phase were measured in the derivation cohort, and only LAGLS at reservoir phase was measured in the validation cohort. In the derivation cohort, EAT thickness was lower in HFrEF/HFmrEF (7.3 ± 2.5 mm) compared to HFpEF (8.3 ± 2.6 mm, p 0.05) and controls (7.9 ± 1.8 mm, p 0.05). Greater EAT thickness was associated with better LV and contractile LA function in HFrEF/HFmrEF, but not in HFpEF (p for interaction0.05). These findings were confirmed in the validation cohort, where EAT thickness was lower in HFrEF/HFmrEF (6.7 ± 1.4 mm) compared to HFpEF (9.6 ± 2.8 mm; p 0.05) and controls (7.7 ± 2.3 mm; p 0.05). Greater EAT thickness was associated with better LV and reservoir LA function in patients with HFrEF/HFmrEF but worse LV and reservoir LA function in patients with HFpEF (p for interaction0.05). Thickened EAT (EAT thickness10 mm) was associated with LA dysfunction (LAGLS at reservoir phase23%) in HFpEF, but not in HFrEF/HFmrEF.Epicardial adipose tissue thickness is greater in patients with HFpEF than HFrEF/HFmrEF. Increased EAT thickness is associated with worse LA and LV function in HFpEF but the opposite in HFrEF/HFmrEF.

Background Heart failure (HF) is a global challenge, with lower- and middle-income countries (LMICs) carrying a large share of the burden. Treatment for HF with reduced ejection fraction (HFrEF) improves survival but is often underused. Economic factors might have an important effect on the use of medicines. Methods and results This analysis assessed prescription rates and doses of renin–angiotensin system (RAS) inhibitors, β-blockers, and mineralocorticoid receptor antagonists at discharge and 6-month follow-up in 8669 patients with HFrEF (1458 from low-, 3363 from middle-, and 3848 from high-income countries) hospitalized for acute HF in 44 countries in the prospective REPORT-HF study. We investigated determinants of guideline-recommended treatments and their association with 1-year mortality, correcting for treatment indication bias. Only 37% of patients at discharge and 34% of survivors at 6 months were on all three medication classes, with lower proportions in LMICs than high-income countries (19 vs. 41% at discharge and 15 vs. 37% at 6 months). Women and patients without health insurance, or from LMICs, or without a scheduled medical follow-up within 6 months of discharge were least likely to be on guideline-recommended medical therapy at target doses, independent of confounders. Being on ≥50% of guideline-recommended doses of RAS inhibitors, and β-blockers were independently associated with better 1-year survival, regardless of country income level. Conclusion Patients with HFrEF in LMICs are less likely to receive guideline-recommended drugs at target doses. Improved access to medications and medical care could reduce international disparities in outcome.

Background: Heart failure is a global public health problem, affecting a large number of individuals from low-income and middle-income countries. REPORT-HF is, to our knowledge, the first prospective global registry collecting information on patient characteristics, management, and prognosis of acute heart failure using a single protocol. The aim of this study was to investigate differences in 1-year post-discharge mortality according to region, country income, and income inequality. Methods: Patients were enrolled during hospitalisation for acute heart failure from 358 centres in 44 countries on six continents. We stratified countries according to a modified WHO regional classification (Latin America, North America, western Europe, eastern Europe, eastern Mediterranean and Africa, southeast Asia, and western Pacific), country income (low, middle, high) and income inequality (according to tertiles of Gini index). Risk factors were identified on the basis of expert opinion and knowledge of the literature. Findings: Of 18 102 patients discharged, 3461 (20%) died within 1 year. Important predictors of 1-year mortality were old age, anaemia, chronic kidney disease, presence of valvular heart disease, left ventricular ejection fraction phenotype (heart failure with reduced ejection fraction [HFrEF] vs preserved ejection fraction [HFpEF]), and being on guideline-directed medical treatment (GDMT) at discharge (p$12 235 per capita) or lower income inequality (ie, from the lowest Gini tertile). Compared with patients with HFrEF, patients with HFpEF had a lower 1-year mortality with little variation by income level (pinteraction for HFrEF vs HFpEF

Visual Abstract, Highlights • The lean diabetic SKO mouse represents a novel and validated murine model of HFpEF. • The SKO HFpEF mouse model recapitulates the cardiac structure and function abnormalities in lean diabetic HFpEF patients in Asia. • Altered cellular titin phosphorylation and increased extracellular interstitial fibrosis associated with neutrophil extracellular traps contribute to the left ventricular stiffness. • Metabolic disturbances arising from insulin resistance and diabetes in the absence of hypertension or obesity may lead to HFpEF., Summary The lean diabetic patients with heart failure with preserved ejection fraction (HFpEF) in Asia suffer from adverse clinical outcomes and poor life quality. The suitable animal models are urgently needed for mechanistic study and therapeutic innovations. Our study reports that lipodystrophic mice with seipin depletion are lean, diabetic, and recapitulate major manifestations of clinical HFpEF, thereby clarifying that lean diabetes per se may produce HFpEF characteristics. We further demonstrate that increased cardiac titin phosphorylation and reactive interstitial fibrosis associated with neutrophil extracellular traps lead to left ventricular stiffness and suggest that both pathways may be potential therapeutic targets in Asian HFpEF patients.

Background Data on rehospitalizations for heart failure (HF) in Asia are scarce. We sought to determine the burden and predictors of HF (first and recurrent) rehospitalizations and all‐cause mortality in patients with HF and preserved versus reduced ejection fraction (preserved EF, ≥50%; reduced EF, Methods and Results Patients with symptomatic (stage C) chronic HF were followed up for death and recurrent HF hospitalizations for 1 year. Predictors of HF hospitalizations or all‐cause mortality were examined with Cox regression for time to first event and other methods for recurrent events analyses. Among 1666 patients with HF with preserved EF (mean age, 68±12 years; 50% women), and 4479 with HF with reduced EF (mean age, 61±13 years; 22% women), there were 642 and 2302 readmissions, with 28% and 45% attributed to HF, respectively. The 1‐year composite event rate for first HF hospitalization or all‐cause death was 11% and 21%, and for total HF hospitalization and all‐cause death was 17.7 and 38.7 per 100 patient‐years in HF with preserved EF and HF with reduced EF, respectively. In HF with preserved EF, consistent independent predictors of these clinical end points included enrollment as an inpatient, Southeast Asian location, and comorbid chronic kidney disease or atrial fibrillation. The same variables were predictive of outcomes in HF with reduced EF except atrial fibrillation, and also included Northeast Asian location, older age, elevated heart rate, decreased systolic blood pressure, diabetes, smoking, and non‐usage of beta blockers. Conclusions One‐year HF rehospitalization and mortality rates were high among Asian patients with HF. Predictors of outcomes identified in this study could aid in risk stratification and timely interventions. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01633398.

OBJECTIVEMicrovascular complications are common among patients with diabetes mellitus (DM). The presence of heart failure (HF) is presumed to be due to macrovascular disease (typically HF with reduced ejection fraction [HFrEF] following myocardial infarction). We hypothesized that HF with preserved ejection fraction (HFpEF) in patients with DM may be a manifestation of microvascular disease compared with HFrEF. The objective of this study was to examine the prevalence and association with clinical outcome of microvascular complications in patients with HF and DM.RESEARCH DESIGN AND METHODSWe investigated the prevalence, association with clinical outcome, and cardiac structure and function of microvascular (neuropathy, nephropathy, and retinopathy) complications of DM in 2,800 prospectively enrolled participants with HF and DM (561 with HFpEF) from the Asian Sudden Cardiac Death In Heart Failure (ASIAN-HF) registry.RESULTSA total of 601 (21.5%) participants with DM had microvascular complications. Participants with DM and any (one or more) microvascular complications were more likely to have HFpEF (odds ratio 1.70 [95% CI 1.15–2.50]; P = 0.008). Furthermore, the likelihood of having HFpEF increased with an increasing number of microvascular complications (Ptrend < 0.001). Microvascular complications were associated with more left ventricular (LV) hypertrophy and a greater reduction in quality of life in HFpEF than HFrEF (Pinteraction < 0.001 for all). Compared with participants with DM and without microvascular complications, the adjusted hazard ratio for the composite outcome of all-cause death or HF hospitalization was 1.35 (95% CI 1.04–1.76) for participants with DM and microvascular complications regardless of HF type (Pinteraction = 0.112).CONCLUSIONSDiabetic microvascular disease is more common, and related to greater LV remodeling, more impairment of quality in life, and similar adverse outcomes, in participants with HFpEF compared with HFrEF. HFpEF may be a clinical manifestation of microvascular disease in DM.

Background Few simple risk models, without echocardiography have been developed for patients with heart failure (HF) and preserved left ventricular ejection fraction (LVEF) (HFpEF). Methods To develop a risk score to predict all-cause death for HFpEF patients, we examined 1277 HF patients with LVEF ≥50% and BNP ≥100 pg/ml in the CHART-2 Study, a large-scale prospective cohort study for HF in Japan. We selected the optimal subset of covariates for the score with Cox proportional hazard models and random survival forests (RSF). Results During the median 5.7-year follow-up, 576 deaths occurred. Cox models and RSF analyses consistently indicated age ≥75 years, albumin Conclusions We developed a simple risk score to predict long-term prognosis of HFpEF patients. The 3A3B score, comprising 6 commonly available parameters in daily practice, has potential utility in the risk stratification and management of HFpEF patients.

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/m(2), P-interaction = 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, P-interaction = 0.009]. Sex also modified the relationship between DM and left ventricular geometry (P-interaction = 0.003), whereby DM was associated with amore concentric left ventricular geometry in women than men. Women had lower quality of life than men (P 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.

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 p interaction =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.

Background Transcatheter atrial septal defect (ASD) and patent foramen ovale (PFO) closure might have opposite short- and long-term haemodynamic consequences compared with restricted interatrial shunt creation, which recently emerged as a potential treatment modality for patients with heart failure with preserved ejection fraction (HFpEF). Given the opposing approaches of ASD and PFO closure versus shunt creation, we investigated the early and sustained cardiac structural and functional changes following transcatheter ASD or PFO closure. Methods In this retrospective study, adult secundum-type ASD and PFO patients with complete echocardiography examinations at baseline and at 1‑day and 1‑year follow-up who also underwent transcatheter closure between 2013 and 2017 at the University Medical Centre Groningen, the Netherlands were included. Results Thirty-nine patients (mean age 48 ± standard deviation 16 years, 61.5% women) were included. Transcatheter ASD/PFO closure resulted in an early and persistent decrease in right ventricular systolic and diastolic function. Additionally, transcatheter ASD/PFO closure resulted in an early and sustained favourable response of left ventricular (LV) systolic function, but also in deterioration of LV diastolic function with an increase in LV filling pressure (LVFP), as assessed by echocardiography. Age (β = 0.31, p = 0.009) and atrial fibrillation (AF; β = 0.24, p = 0.03) were associated with a sustained increase in LVFP after transcatheter ASD/PFO closure estimated by mean E/e’ ratio (i.e. ratio of mitral peak velocity of early filling to diastolic mitral annular velocity). In subgroup analysis, this was similar for ASD and PFO closure. Conclusion Older patients and patients with AF were predisposed to sustained increases in left-sided filling pressures resembling HFpEF following ASD or PFO closure. Consequently, these findings support the current concept that creating a restricted interatrial shunt might be beneficial, particularly in elderly HFpEF patients with AF.

Background Angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and beta-blockers are guideline-recommended first-line therapies in heart failure (HF) with reduced ejection fraction (HFrEF). Previous studies showed that individual drug classes were under-dosed in many parts of Europe and Asia. In this study, we investigated the association of combined up-titration of ACEi/ARBs and beta-blockers with all-cause mortality and its combination with hospitalization for HF. Methods and results A total of 6787 HFrEF patients (mean age 62.6 +/- 13.2 years, 77.7% men, mean left ventricular ejection fraction 27.7 +/- 7.2%) were enrolled in the prospective multinational European (BIOSTAT-CHF;n = 2100) and Asian (ASIAN-HF;n = 4687) studies. Outcomes were analysed according to achieved percentage of guideline-recommended target doses (GRTD) of combination ACEi/ARB and beta-blocker therapy, adjusted for indication bias. Only 14% (n = 981) patients achieved >= 50% GRTD for both ACEi/ARB and beta-blocker. The best outcomes were observed in patients who achieved 100% GRTD of both ACEi/ARB and beta-blocker [hazard ratio (HR) 0.32, 95% confidence interval (CI) 0.26-0.39 vs. none]. Lower dose of combined therapy was associated with better outcomes than 100% GRTD of either monotherapy. Up-titrating beta-blockers was associated with a consistent and greater reduction in hazards of all-cause mortality (HR for 100% GRTD: 0.40, 95% CI 0.25-0.63) than corresponding ACEi/ARB up-titration (HR 0.75, 95% CI 0.53-1.07). Conclusion This study shows that best outcomes were observed in patients attaining GRTD for both ACEi/ARB and beta-blockers, unfortunately this was rarely achieved. Achieving >50% GRTD of both drug classes was associated with better outcome than target dose of monotherapy. Up-titrating beta-blockers to target dose was associated with greater mortality reduction than up-titrating ACEi/ARB.

Summary: Background: Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), β blockers, and mineralocorticoid receptor antagonists (MRAs) are of proven benefit and are recommended by guidelines for management of patients with heart failure and reduced ejection fraction (HFrEF). We aimed to examine the first prospective multinational data from Asia on prescribing patterns of guideline-directed medical therapies and analyse its effect on outcomes. Methods: In the prospective multinational ASIAN-HF registry (with enrolment from 46 centres in 11 countries in Asia), we enrolled patients aged 18 years or older, with symptomatic heart failure (stage C, with at least one episode of decompensated heart failure in the past 6 months that resulted in admission to hospital or was treated in an outpatient clinic) and left ventricular systolic dysfunction (ejection fraction ≤40% on baseline echocardiography, consistent with 2016 European Society of Cardiology guidelines). We excluded patients with heart failure caused by severe valvular heart disease, life-threatening comorbidity with a life expectancy of less than 1 year, who were unable or unwilling to give consent, or who had concurrent participation in a clinical trial. Patients were followed up for 3 years for the outcomes of death and cause-specific admittance to hospital. Primary outcomes were uptake of guideline-directed medical therapies (as proportions) by therapeutic class, achieved doses as proportions of guideline-recommended doses, and their association with 1-year composite outcome of all-cause death or admittance to hospital because of heart failure. This study is registered with ClinicalTrials.gov, number NCT01633398. Findings: Between Oct 1, 2012, and Dec 31, 2015, we enrolled 5276 patients with HFrEF (mean age 59·6 years [SD 13·2], 77% men, body-mass index 24·9 kg/m2 [5·1], 33% New York Heart Association class III or IV). Follow-up data were available for 4544 (90%) of 5061 eligible patients taking medication for heart failure, with median follow-up of 417 days (IQR 214–735). ACE inhibitors or ARBs were prescribed to 3868 (77%) of 5005 patients, β blockers to 3975 (79%) of 5061, and MRAs to 2998 (58%) of 5205, with substantial regional variation. Guideline-recommended dose was achieved in only 17% of cases for ACE inhibitors or ARB, 13% for β blockers, and 29% for MRAs. Country (all three drug classes), increasing body-mass index (ACE inhibitors or ARBs and MRAs), and in-patient recruitment (ACE inhibitors or ARBs and β blockers) were associated with attainment of guideline-recommended dose (all p

AIM To describe differences in patient characteristics and outcomes by ethnicity in patients with diabetes mellitus (DM) and heart failure (HF) with reduced ejection fraction (HFrEF, ejection fraction ≤35%) in a multi-ethnic cohort. METHODS AND RESULTS Patient level data from two cohorts (HF-ACTION and ASIAN-HF) were combined, and patients grouped by self-reported ethnicity. DM was defined as the presence of a clinical diagnosis and/or receiving anti-diabetic therapy. A total of 6214 (1324 whites, 674 blacks, 1297 Chinese, 1510 Indians, 717 Malays, 692 Japanese/Koreans) patients were included. The overall prevalence of DM was 39.5% (n = 2454). The prevalence of DM was lowest in whites (29.3%), followed by Japanese/Koreans (34.1%), blacks (35.9%), Chinese (42.3%), Indians (44.2%), and highest in Malays (51.9%). The correlation between age, sex, body mass index, coronary artery disease, hypertension, atrial fibrillation, peripheral vascular disease and chronic kidney disease with DM differed significantly by ethnicity (P for interaction

Objectives/Background In heart failure (HF), pulse pressure (PP) may reflect both vascular stiffness and left ventricular function, but its prognostic role in relation to ejection fraction (EF) is poorly understood. Methods In the Swedish Heart Failure Registry, we investigated the association between PP and 1-year mortality in patients with HF and reduced (HFrEF, Results Among 36,770 patients discharged alive or enrolled as out-patients with 1-year follow-up (mean age 74±12years, 63% men, 56% HFrEF, 21% HFmrEF, 23% HFpEF), crude one-year mortality was 18%. Mean PP increased across EF groups: 51±16 in HFrEF, 57±18 in HFmrEF, 60±19mmHg in HFpEF. In crude regression splines, the association between PP and mortality was U-shaped in HFmrEF and HFpEF, but curvilinear with only low PP associated with mortality in HFrEF. In multivariable analyses, a significant interaction by EF group and PP was observed (p interaction =0.015): low PP was associated with higher mortality in HFrEF (adjusted OR [1st vs. 4th quintile]=1.40, 95% CI 1.18–1.67) and HFpEF (1.43, 1.14–1.81) but only by trend in HFmrEF; high PP had a trend towards higher mortality in HFmrEF (5th vs. 3rd quintile=1.30, 1.00–1.69) and HFpEF (1.25, 0.98–1.61). Conclusions The association between PP and mortality in HF was influenced by EF. Low PP was independently associated with mortality in HFrEF and HFpEF and by trend in HFmrEF. High PP was independently associated with mortality by trend in HFmrEF and HFpEF.

Aims N-terminal pro-B-type natriuretic peptide (NT-proBNP) is the most frequently used biomarker in heart failure (HF), but its prognostic utility across ethnicities is unclear. Methods and results This study included 546 Caucasians with HF from the Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure and 578 Asians with HF from the Singapore Heart Failure Outcomes and Phenotypes study. NT-proBNP was measured at discharge after HF hospitalization. The studied outcome was a composite of all-cause mortality and HF hospitalization at 18 months. Compared with Caucasian patients, Asian patients were younger (63 +/- 12 vs. 71 +/- 11 years); less often female (26% vs. 39%); and had lower body mass index (26 vs. 27 kg/m(2)), better renal function (61 +/- 37 vs. 54 +/- 20 mL/min/1.73 m(2)), lower rates of atrial fibrillation (25% vs. 46%), strikingly higher rates of diabetes (59% vs. 30%), and higher rates of hypertension (76% vs. 44%). Despite these clear inter-group differences in individual drivers of NT-proBNP, average levels were similar in Asians [2709 (1350, 6302) pg/mL] and Caucasians [2545 (1308, 5484) pg/mL] (P = 0.514). NT-proBNP was strongly associated with outcome [hazard ratio 1.28 (per doubling), 95% confidence interval 1.18-1.39, P

IntroductionDiabetes mellitus is a growing public health epidemic in Asia. We examined the impact of type 2 diabetes, glycemic control and microvascular complications on mortality and cardiovascular outcomes in a multiethnic population-based cohort of Asians without prior cardiovascular disease.Research design and methodsThis was a prospective population-based cohort study in Singapore comprising participants from the three major Asian ethnic groups: Chinese, Malays and Indians, with baseline examination in 2004–2011. Participants with type 1 diabetes and those with cardiovascular disease at baseline were excluded. Type 2 diabetes, Hemoglobin A1c (HbA1c) levels and presence of microvascular complications (diabetic retinopathy and nephropathy) were defined at baseline. The primary outcome was all-cause mortality and major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular mortality, myocardial infarction, stroke and revascularization, collected using a national registry.ResultsA total of 8541 subjects were included, of which 1890 had type 2 diabetes at baseline. Subjects were followed for a median of 6.4 (IQR 4.8–8.8) years. Diabetes was a significant predictor of mortality (adjusted HR 1.74, 95% CI 1.45 to 2.08, pConclusionDiabetes is a significant predictor of mortality and cardiovascular morbidity in Asian patients without prior cardiovascular disease. Among patients with type 2 diabetes, poorer glycemic control was associated with increased MACE but not mortality rates. Greater burden of microvascular complications identified a subset of patients with poorer outcomes.