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

Tromp J, Tay WT, Ouwerkerk W, Teng TK, Yap J, MacDonald MR, et al.

PLoS Med, 2018 03;15(3):e1002541.
PMID: 29584721 DOI: 10.1371/journal.pmed.1002541

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

MacDonald MR, Tay WT, Teng TK, Anand I, Ling LH, Yap J, et al.

J Am Heart Assoc, 2020 01 07;9(1):e012199.
PMID: 31852421 DOI: 10.1161/JAHA.119.012199

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

Chandramouli C, Tay WT, Bamadhaj NS, Tromp J, Teng TK, Yap JJL, et al.

PLoS Med, 2019 09;16(9):e1002916.
PMID: 31550265 DOI: 10.1371/journal.pmed.1002916

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

Chyou JY, Tay WT, Anand IS, Teng TK, Yap JJL, MacDonald MR, et al.

J Am Heart Assoc, 2021 03 16;10(6):e017932.
PMID: 33719492 DOI: 10.1161/JAHA.120.017932

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

Chia YMF, Teng TK, Tan ESJ, Tay WT, Richards AM, Chin CWL, et al.

Circ Cardiovasc Qual Outcomes, 2017 Nov;10(11).
PMID: 29150533 DOI: 10.1161/CIRCOUTCOMES.116.003651

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.