Hean Yee Ong

Iron deficiency in a multi-ethnic Asian population with and without heart failure: prevalence, clinical correlates, functional significance and prognosis

Current heart failure (HF) guidelines highlight the importance of iron deficiency (ID) in HF. Whether HF itself or age‐related comorbidities contribute to ID is uncertain, and previous data were limited to Western populations. We aimed to study the prevalence, clinical correlates, functional significance and prognosis of ID in HF patients, compared with community‐based controls in a multi‐ethnic Southeast Asian population.

The Singapore Heart Failure Outcomes and Phenotypes (SHOP) Study and Prospective Evaluation of Outcome in Patients With Heart Failure With Preserved Left Ventricular Ejection Fraction (PEOPLE) Study: Rationale and Design

BACKGROUND Heart failure (HF) with preserved ejection fraction (EF) accounts for a substantial proportion of cases of HF, and to date no treatments have clearly improved outcome. There are also little data comparing HF cohorts of differing ethnicity within the Asia-Pacific region. METHODS The Singapore Heart Failure Outcomes and Phenotypes (SHOP) study and Prospective Evaluation of Outcome in Patients with Heart Failure with Preserved Left Ventricular Ejection Fraction (PEOPLE) study are parallel prospective studies using identical protocols to enroll patients with HF across 6 centers in Singapore and 4 in New Zealand. The objectives are to determine the relative prevalence, characteristics, and outcomes of patients with HF and preserved EF (EF ≥50%) compared with those with HF and reduced EF, and to determine initial data on ethnic differences within and between New Zealand and Singapore. Case subjects (n = 2,500) are patients hospitalized with a primary diagnosis of HF or attending outpatient clinics for management of HF within 6 months of HF decompensation. Control subjects are age- and gender-matched community-based adults without HF from Singapore (n = 1,250) and New Zealand (n = 1,073). All participants undergo detailed clinical assessment, echocardiography, and blood biomarker measurements at baseline, 6 weeks, and 6 months, and are followed over 2 years for death or hospitalization. Substudies include vascular assessment, cardiopulmonary exercise testing, retinal imaging, and cardiac magnetic resonance imaging. CONCLUSIONS The SHOP and PEOPLE studies are the first prospective multicenter studies defining the epidemiology and interethnic differences among patients with HF in the Asia-Oceanic region, and will provide unique insights into the pathophysiology and outcomes for these patients.

Right ventricular dysfunction in left-sided heart failure with preserved versus reduced ejection fraction

Right ventricular (RV) dysfunction is recognized as a major prognostic factor in left‐sided heart failure (HF). However, the relative contribution of RV dysfunction in HF with preserved (HFpEF) vs. reduced ejection fraction (HFrEF) is unclear.

Recalibration of the Global Registry of Acute Coronary Events risk score in a multiethnic Asian population

BACKGROUND Acute myocardial infarction (AMI) is a leading cause of mortality in Asia. However, quantitative risk scores to predict mortality after AMI were developed without the participation of Asian countries. METHODS We evaluated the performance of the Global Registry of Acute Coronary Events (GRACE) in-hospital mortality risk score, directly and after recalibration, in a large Singaporean cohort representing 3 major Asian ethnicities. RESULTS The GRACE cohort included 11,389 patients, predominantly of European descent, hospitalized for AMI or unstable angina from 2002 to 2003. The Singapore cohort included 10,100 Chinese, 3,005 Malay, and 2,046 Indian patients hospitalized for AMI from 2002 to 2005.Using the original GRACE score, predicted in-hospital mortality was 2.4% (Chinese), 2.0% (Malay), and 1.6% (Indian). However, observed in-hospital mortality was much greater at 9.8% (Chinese), 7.6% (Malay), and 6.4% (Indian). The c statistic for Chinese, Malays, and Indians was 0.86, 0.86, and 0.84, respectively, and the Hosmer-Lemeshow statistic was 250, 56, and 41, respectively. Recalibration of the GRACE score, using the mean-centered constants derived from the Singapore cohort, did not change the c statistic but substantially improved the Hosmer-Lemeshow statistic to 90, 24, and 18, respectively. The recalibrated GRACE score predicted in-hospital mortality as follows: 7.7% (Chinese), 6.0% (Malay), and 5.2% (Indian). CONCLUSION In this large cohort of 3 major Asian ethnicities, the original GRACE score, derived from populations outside Asia, underestimated in-hospital mortality after AMI. Recalibration improved risk estimation substantially and may help adapt externally developed risk scores for local practice.

Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international multi-ethnic cohort study

Aims Whether prevalence and mortality of patients with heart failure with preserved or mid-range (40-49%) ejection fraction (HFpEF and HFmREF) are similar to those of heart failure with reduced ejection fraction (HFrEF), as reported in some epidemiologic studies, remains highly controversial. We determined and compared characteristics and outcomes for patients with HFpEF, HFmREF, and HFrEF in a prospective, international, multi-ethnic population. Methods and results Prospective multi-centre longitudinal study in New Zealand (NZ) and Singapore. Patients with HF were assessed at baseline and followed over 2 years. The primary outcome was death from any cause. Secondary outcome was death and HF hospitalization. Cox proportional hazards models were used to compare outcomes for patients with HFpEF, HFmrEF, and HFrEF. Of 2039 patients enrolled, 28% had HFpEF, 13% HFmrEF, and 59% HFrEF. Compared with HFrEF, patients with HFpEF were older (62 vs. 72 years), more commonly female (17% vs. 48%), and more likely to have a history of hypertension (61% vs. 78%) but less likely to have coronary artery disease (55% vs. 41%). During 2 years of follow-up, 343 (17%) patients died. Adjusting for age, sex, and clinical risk factors, patients with HFpEF had a lower risk of death compared with those with HFrEF (hazard ratio 0.62, 95% confidence interval 0.46-0.85). Plasma (NT-proBNP) was similarly related to mortality in both HFpEF, HFmrEF, and HFrEF independent of the co-variates listed and of ejection fraction. Results were similar for the composite endpoint of death or HF and were consistent between Singapore and NZ. Conclusion These prospective multinational data showed that the prevalence of HFpEF within the HF population was lower than HFrEF. Death rate was comparable in HFpEF and HFmrEF and lower than in HFrEF. Plasma levels of NT-proBNP were independently and similarly predictive of death in the three HF phenotypes. Trial Registration Australian New Zealand Clinical Trial Registry (ACTRN12610000374066).

Circadian Dependence of Infarct Size and Acute Heart Failure in ST Elevation Myocardial Infarction

Objectives There are conflicting data on the relationship between the time of symptom onset during the 24-hour cycle (circadian dependence) and infarct size in ST-elevation myocardial infarction (STEMI). Moreover, the impact of this circadian pattern of infarct size on clinical outcomes is unknown. We sought to study the circadian dependence of infarct size and its impact on clinical outcomes in STEMI. Methods We studied 6,710 consecutive patients hospitalized for STEMI from 2006 to 2009 in a tropical climate with non-varying day-night cycles. We categorized the time of symptom onset into four 6-hour intervals: midnight–6:00 A.M., 6:00 A.M.–noon, noon–6:00 P.M. and 6:00 P.M.–midnight. We used peak creatine kinase as a surrogate marker of infarct size. Results Midnight–6:00 A.M patients had the highest prevalence of diabetes mellitus (P = 0.03), more commonly presented with anterior MI (P = 0.03) and received percutaneous coronary intervention less frequently, as compared with other time intervals (P = 0.03). Adjusted mean peak creatine kinase was highest among midnight–6:00 A.M. patients and lowest among 6:00 A.M.–noon patients (2,590.8±2,839.1 IU/L and 2,336.3±2,386.6 IU/L, respectively, P = 0.04). Midnight–6:00 A.M patients were at greatest risk of acute heart failure (P<0.001), 30-day mortality (P = 0.03) and 1-year mortality (P = 0.03), while the converse was observed in 6:00 A.M.–noon patients. After adjusting for diabetes, infarct location and performance of percutaneous coronary intervention, circadian variations in acute heart failure incidence remained strongly significant (P = 0.001). Conclusion We observed a circadian peak and nadir in infarct size during STEMI onset from midnight–6:00A.M and 6:00A.M.–noon respectively. The peak and nadir incidence of acute heart failure paralleled this circadian pattern. Differences in diabetes prevalence, infarct location and mechanical reperfusion may account partly for the observed circadian pattern of infarct size and acute heart failure.

The prognostic value of highly sensitive cardiac troponin assays for adverse events in men and women with stable heart failure and a preserved vs. reduced ejection fraction

Circulating biomarkers are important in the diagnosis, risk stratification and management of patients with heart failure (HF). Given the current lack of biomarkers in HF with preserved ejection fraction (HFpEF), we aimed to investigate the prognostic performance of the newly developed high‐sensitivity (hs) assays for cardiac troponin I (hsTnI) compared with troponin T (hsTnT) for adverse events in HFpEF vs. HF with reduced ejection fraction (HFrEF). Findings in these two HF subgroups were also compared with those in the recently defined HF with mid‐range ejection fraction (HFmrEF) subgroup.

Ethnic differences in the association of QRS duration with ejection fraction and outcome in heart failure

Background QRS duration (QRSd) criteria for device therapy in heart failure (HF) were derived from predominantly white populations and ethnic differences are poorly understood. Methods We compared the association of QRSd with ejection fraction (EF) and outcomes between 839 Singaporean Asian and 11 221 Swedish white patients with HF having preserved EF (HFPEF)and HF having reduced EF (HFREF) were followed in prospective population-based HF studies. Results Compared with whites, Asian patients with HF were younger (62 vs 74 years, p<0.001), had smaller body size (height 163 vs 171 cm, weight 70 vs 80 kg, both p<0.001) and had more severely impaired EF (EF was <30% in 47% of Asians vs 28% of whites). Overall, unadjusted QRSd was shorter in Asians than whites (101 vs 104 ms, p<0.001). Lower EF was associated with longer QRSd (p<0.001), with a steeper association among Asians than whites (pinteraction<0.001), independent of age, sex and clinical covariates (including body size). Excluding patients with left bundle branch block (LBBB) and adjusting for clinical covariates, QRSd was similar in Asians and whites with HFPEF, but longer in Asians compared with whites with HFREF (p=0.001). Longer QRSd was associated with increased risk of HF hospitalisation or death (absolute 2-year event rate for ≤120 ms was 40% and for >120 ms it was 52%; HR for 10 ms increase of QRSd was 1.04 (1.03 to 1.06), p<0.001), with no interaction by ethnicity. Conclusion We found ethnic differences in the association between EF and QRSd among patients with HF. QRS prolongation was similarly associated with increased risk, but the implications for ethnicity-specific QRSd cut-offs in clinical decision-making require further study.

Influence of Ethnicity, Age, and Time on Sex Disparities in Long‐Term Cause‐Specific Mortality After Acute Myocardial Infarction

Background We examined the influence of sex, ethnicity, and time on competing cardiovascular and noncardiovascular causes of death following acute myocardial infarction in a multiethnic Asian cohort. Methods and Results For 12 years, we followed a prospective nationwide cohort of 15 151 patients (aged 22–101 years, median age 63 years; 72.3% male; 66.7% Chinese, 19.8% Malay, 13.5% Indian) who were hospitalized for acute myocardial infarction between 2000 and 2005. There were 6463 deaths (4534 cardiovascular, 1929 noncardiovascular). Compared with men, women had a higher risk of cardiovascular death (age‐adjusted hazard ratio [HR] 1.3, 95% CI 1.2–1.4) but a similar risk of noncardiovascular death (HR 0.9, 95% CI 0.8–1.0). Sex differences in cardiovascular death varied by ethnicity, age, and time. Compared with Chinese women, Malay women had the greatest increased hazard of cardiovascular death (HR 1.4, 95% CI 1.2–1.6) and a marked imbalance in death due to heart failure or cardiomyopathy (HR 3.4 [95% CI 1.9–6.0] versus HR 1.5 [95% CI 0.6–3.6] for Indian women). Compared with same‐age Malay men, Malay women aged 22 to 49 years had a 2.5‐fold (95% CI 1.6–3.8) increased hazard of cardiovascular death. Sex disparities in cardiovascular death tapered over time, least among Chinese patients and most among Indian patients; the HR comparing cardiovascular death of Indian women and men decreased from 1.9 (95% CI 1.5–2.4) at 30 days to 0.9 (95% CI 0.5–1.6) at 10 years. Conclusion Age, ethnicity, and time strongly influence the association between sex and specific cardiovascular causes of mortality, suggesting that health care policy to reduce sex disparities in acute myocardial infarction outcomes must consider the complex interplay of these 3 major modifying factors.

N-terminal pro-B-type natriuretic peptide and prognosis in Caucasian vs. Asian patients with heart failure: Ethnicity and NT-proBNP in heart failure

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.