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

Luo N, Teng TK, Tay WT, Anand IS, Kraus WE, Liew HB, et al.

Am Heart J, 2017 Sep;191:75-81.
PMID: 28888273 DOI: 10.1016/j.ahj.2017.06.016

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

Goh VJ, Tromp J, Teng TK, Tay WT, Van Der Meer P, Ling LH, et al.

ESC Heart Fail, 2018 08;5(4):570-578.
PMID: 29604185 DOI: 10.1002/ehf2.12279

AIMS: 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.
METHODS AND RESULTS: We prospectively studied 3886 Asian patients (60 ± 13 years, 21% women) with HF (ejection fraction ≤40%) from 11 regions in the Asian Sudden Cardiac Death in Heart Failure study. Anaemia was defined as haemoglobin <13 g/dL (men) and <12 g/dL (women). Ethnic groups included Chinese (33.0%), Indian (26.2%), Malay (15.1%), Japanese/Korean (20.2%), and others (5.6%). Overall, anaemia was present in 41%, with a wide range across ethnicities (33-54%). Indian ethnicity, older age, diabetes, and chronic kidney disease were independently associated with higher odds of anaemia (all P HF hospitalization at 1 year (hazard ratio = 1.28, 95% CI 1.08-1.50) compared with non-anaemic patients. The prognostic impact of anaemia was modified by ethnicity (Pinteraction = 0.02), with the greatest hazard ratio in Japanese/Koreans (1.82; 95% CI 1.14-2.91).
CONCLUSIONS: Anaemia is present in a third to more than half of Asian patients with HF and adversely impacts quality of life and survival. Ethnic differences exist wherein prevalence is highest among Indians, and survival is most severely impacted by anaemia in Japanese/Koreans.
Heart failure with preserved ejection fraction in Asia

Tromp J, Teng TH, Tay WT, Hung CL, Narasimhan C, Shimizu W, et al.

Eur J Heart Fail, 2019 01;21(1):23-36.
PMID: 30113120 DOI: 10.1002/ejhf.1227

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

METHODS AND RESULTS: We prospectively studied clinical characteristics, echocardiographic parameters and outcomes in 1204 patients with HFpEF (left ventricular ejection fraction ≥50%) from 11 Asian regions, grouped as Northeast Asia (Hong Kong, Taiwan, China, Japan, Korea, n = 543), South Asia (India, n = 252), and Southeast Asia (Malaysia, Thailand, Singapore, Indonesia, Philippines, n = 409). Mean age was 68 ±12 years (37% were Asian patients had the highest prevalence of all co-morbidities except atrial fibrillation, South Asians had the lowest prevalence of all co-morbidities except anaemia and obesity, and Northeast Asians had more atrial fibrillation. Left ventricular hypertrophy and concentric remodelling were most prominent among Southeast and South Asians, respectively (P Asians were at higher risk for adverse outcomes, independent of co-morbidity burden and cardiac geometry.

CONCLUSION: These first prospective multinational data from Asia show that HFpEF affects relatively young patients with a high burden of co-morbidities. Regional differences in types of co-morbidities, cardiac remodelling and outcomes of HFpEF across Asia have important implications for public health measures and global HFpEF trial design.