Wan Ting Tay

A comprehensive population‐based characterization of heart failure with mid‐range ejection fraction

Clinical features and outcomes in the novel phenotype heart failure with mid‐range ejection fraction [HFmrEF, ejection fraction (EF) 40–49%] were compared with heart failure with reduced EF (HFrEF, EF <40%) and preserved EF (HFpEF, EF ≥50%).

Significance of Ischemic Heart Disease in Patients with Heart Failure and Preserved, Midrange, and Reduced Ejection Fraction : A Nationwide Cohort Study

Background— The pathogenic role of ischemic heart disease (IHD) in heart failure (HF) with reduced ejection fraction (HFrEF; EF <40%) is well established, but its pathogenic and prognostic significance in HF with midrange (HFmrEF; EF 40%–50%) and preserved EF (HFpEF; EF ≥50%) has been much less explored. Methods and Results— We evaluated 42 987 patients from the Swedish Heart Failure Registry with respect to baseline IHD, outcomes (IHD, HF, cardiovascular events, and all-cause death), and EF change during a median follow-up of 2.2 years. Overall, 23% had HFpEF (52% IHD), 21% had HFmrEF (61% IHD), and 55% had HFrEF (60% IHD). After multivariable adjustment, associations with baseline IHD were similar for HFmrEF and HFrEF and lower in HFpEF (risk ratio, 0.91 [0.89–0.93] versus HFmrEF and risk ratio, 0.90 [0.88–0.92] versus HFrEF). The adjusted risk of IHD events was similar for HFmrEF versus HFrEF and lower in HFpEF (hazard ratio, 0.89 [0.84–0.95] versus HFmrEF and hazard ratio, 0.84 [0.80–0.90] versus HFrEF). After adjustment, prevalent IHD was associated with increased risk of IHD events and all other outcomes in all EF categories except all-cause mortality in HFpEF. Those with IHD, particularly new IHD events, were also more likely to change to a lower EF category and less likely to change to a higher EF category over time. Conclusions— HFmrEF resembled HFrEF rather than HFpEF with regard to both a higher prevalence of IHD and a greater risk of new IHD events. Established IHD was an important prognostic factor across all HF types.

Multinational and multiethnic variations in health-related quality of life in patients with chronic heart failure

Background Assessing health‐related quality of life (HRQoL) in patients with heart failure (HF) is an important goal of clinical care and HF research. We sought to investigate ethnic differences in perceived HRQoL and its association with mortality among patients with HF and left ventricular ejection fraction ≤35%, controlling for demographic characteristics and HF severity. Methods and results We compared 5697 chronic HF patients of Indian (26%), white (23%), Chinese (17%), Japanese/Koreans (12%), black (12%), and Malay (10%) ethnicities from the HF‐ACTION and ASIAN‐HF multinational studies using the Kansas City Cardiomyopathy Questionnaire (KCCQ; range 0–100; higher scores reflect better health status). KCCQ scores were lowest in Malay (58 ± 22) and Chinese (60 ± 23), intermediate in black (64 ± 21) and Indian (65 ± 23), and highest in white (67 ± 20) and Japanese or Korean patients (67 ± 22) after adjusting for age, sex, educational status, HF severity, and risk factors. Self‐efficacy, which measures confidence in the ability to manage symptoms, was lower in all Asian ethnicities (especially Japanese/Koreans [60 ± 26], Malay [66 ± 23], and Chinese [64 ± 28]) compared to black (80 ± 21) and white (82 ± 19) patients, even after multivariable adjustment (P < .001). In all ethnicities, KCCQ strongly predicted 1‐year mortality (HR 0.45, 95% CI 0.30–0.67 for highest vs lowest quintile of KCCQ; P for interaction by ethnicity .101). Conclusions Overall, HRQoL is inversely and independently related to mortality in chronic HF but is not modified by ethnicity. Nevertheless, ethnic differences exist independent of HF severity and comorbidities. These data may have important implications for future global clinical HF trials that use patient‐reported outcomes as endpoints.

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

Different relationships between pulse pressure and mortality in heart failure with reduced, mid-range and preserved ejection fraction

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, <40%), mid-range (HFmrEF, 40-49%) and preserved EF (HFpEF, ≥50%), using multivariable logistic regression and restricted cubic splines. 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 (pinteraction=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.

Heart failure with preserved ejection fraction in Asia: HFpEF in Asia

Heart failure with preserved ejection fraction (HFpEF) is a global public health problem. Unfortunately, little is known about HFpEF across Asia.

Prevalence, clinical correlates, and outcomes of anaemia in multi-ethnic Asian patients with heart failure with reduced ejection fraction: Anaemia in multi-ethnic Asian patients with heart failure with reduced ejection fraction

Recent international heart failure (HF) guidelines recognize anaemia as an important comorbidity contributing to poor outcomes in HF, based on data mainly from Western populations. We sought to determine the prevalence, clinical correlates, and prognostic impact of anaemia in patients with HF with reduced ejection fraction across Asia.

Disparity Between Indications for and Utilization of Implantable Cardioverter Defibrillators in Asian Patients With Heart Failure

Background— Implantable cardioverter defibrillators (ICDs) are lifesaving devices for patients with heart failure (HF) and reduced ejection fraction. However, utilization and determinants of ICD insertion in Asia are poorly defined. We determined the utilization, associations of ICD uptake, patient-perceived barriers to device therapy and, impact of ICDs on mortality in Asian patients with HF. Methods and Results— Using the prospective ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) registry, 5276 patients with symptomatic HF and reduced ejection fraction (HFrEF) from 11 Asian regions and across 3 income regions (high: Hong Kong, Japan, Korea, Singapore, and Taiwan; middle: China, Malaysia, and Thailand; and low: India, Indonesia, and Philippines) were studied. ICD utilization, clinical characteristics, as well as device perception and knowledge, were assessed at baseline among ICD-eligible patients (EF ⩽35% and New York Heart Association Class II-III). Patients were followed for the primary outcome of all-cause mortality. Among 3240 ICD-eligible patients (mean age 58.9±12.9 years, 79.1% men), 389 (12%) were ICD recipients. Utilization varied across Asia (from 1.5% in Indonesia to 52.5% in Japan) with a trend toward greater uptake in regions with government reimbursement for ICDs and lower out-of-pocket healthcare expenditure. ICD (versus non-ICD) recipients were more likely to be older (63±11 versus 58±13 year; P<0.001), have tertiary (versus ⩽primary) education (34.9% versus 18.1%; P<0.001) and be residing in a high (versus low) income region (64.5% versus 36.5%; P<0.001). Among 2000 ICD nonrecipients surveyed, 55% were either unaware of the benefits of, or needed more information on, device therapy. ICD implantation reduced risks of all-cause mortality (hazard ratio, 0.71; 95% confidence interval, 0.52–0.97) and sudden cardiac deaths (hazard ratio, 0.33; 95% confidence interval, 0.14–0.79) over a median follow-up of 417 days. Conclusions— ICDs reduce mortality risk, yet utilization in Asia is low; with disparity across geographic regions and socioeconomic status. Better patient education and targeted healthcare reforms in extending ICD reimbursement may improve access. Clinical Trial Registration— URL: https://clinicaltrials.gov/ct2/show/NCT01633398. Unique identifier: NCT01633398.

Prescribing patterns of evidence-based heart failure pharmacotherapy and outcomes in the ASIAN-HF registry: a cohort study

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<0·05). When adjusted for indication bias, increasing drug doses, from low dose (1-<25% of guideline-recommended dose) upwards were associated with lower hazards of a 1-year composite outcome for ACE inhibitors or ARBs and β blockers compared with non-users. The lowest adjusted hazards were in the group that attained guideline-recommended doses above 50% (hazard ratio [HR] 0·54, 95% CI 0·50-0·58 for ACE inhibitors or ARBs [50-99·9%]; HR 0·47, 0·46-0·50 for β blockers, and HR 0·77, 0·72-0·81 for MRAs [≥100%]). INTERPRETATION Guideline-directed medical therapies at recommended doses are underutilised in patients with HFrEF. Improved uptake and uptitration of guideline-directed medical therapies are needed for better patient outcomes. FUNDING National Medical Research Council (Singapore), A*STAR Biomedical Research Council ATTRaCT program, Boston Scientific Investigator Sponsored Research program, and Bayer.

The 3A3B score: The simple risk score for heart failure with preserved ejection fraction - A report from the CHART-2 Study

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 <3.7 g/dl, anemia, BMI <22 kg/m2, BNP ≥300 pg/ml (or NT-proBNP ≥1400 pg/ml), and BUN ≥25 mg/dl, as the important 6 prognostic variables. Incorporating these 6 variables, we developed a scoring system (3A3B score, with 2 points given to age ≥75 years and 1 point to the others based on the hazard ratios. The discrimination ability of the risk score was excellent (c-index 0.708). Regarding model goodness-of-fit, the overall gradient in 5-year risk was well captured by the score. The predictive accuracy of the 3A3B score was confirmed in the external validation cohorts from the TOPCAT trial (N = 835, c-index 0.652) and the ASIAN-HF registry (N = 170, c-index 0.741). 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.