Fazlur Jaufeerally

Growth differentiation factor 15, ST2, high‐sensitivity troponin T, and N‐terminal pro brain natriuretic peptide in heart failure with preserved vs. reduced ejection fraction

Growth differentiation factor 15 (GDF15), ST2, high‐sensitivity troponin T (hsTnT), and N‐terminal pro brain natriuretic peptide (NT‐proBNP) are biomarkers of distinct mechanisms that may contribute to the pathophysiology of heart failure (HF) [inflammation (GDF15); ventricular remodelling (ST2); myonecrosis (hsTnT); and wall stress (NT‐proBNP)].

Growth differentiation factor 15 in heart failure with preserved vs. reduced ejection fraction.

Growth differentiation factor 15 (GDF15) is a cytokine highly expressed in states of inflammatory stress. We aimed to study the clinical correlates and prognostic significance of plasma GDF15 in heart failure with preserved ejection fraction (HFpEF) vs. reduced ejection fraction(HFrEF), compared with N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), an indicator of haemodynamic wall stress.

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.

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).

Predictors of two-year mortality in Asian patients with heart failure and preserved ejection fraction

INTRODUCTION Mortality in patients with heart failure and preserved ejection fraction (HFpEF) remains high. Data from Asia is lacking. We aim to study the impact of ethnicity and other predictors of mortality in patients admitted for HFpEF in a multi-ethnic Asian country. MATERIAL AND METHODS Consecutive patients admitted to two local institutions with heart failure and ejection fraction ≥50% on transthoracic echocardiogram from Jan 2008 to Dec 2009 were included. All patients were followed-up for 2 years. Overall mortality was obtained from the national registry of deaths in our country. RESULTS A total of 1960 patients with heart failure were included. 751 (38.3%) patients had HFpEF. Overall mortality at two years was 26.6% (n=200) compared to 37.1% (n=449) in patients with reduced ejection fraction (HR 0.618 (95% CI 0.508-0.753), p<0.001). Ethnicity did not predict mortality. On multivariable Cox regression analysis, significant predictors of two-year mortality in HFpEF patients were older age (HR 1.027 (1.011-1.044)), prior myocardial infarction (HR 1.577 (1.104-2.253)), prior stroke (HR 1.475 (1.055-2.061)), smoking (HR 1.467 (1.085-1.985)), higher creatinine levels (HR 1.002 (1.001-1.003)) and use of mineralocorticoid receptor antagonists (HR 1.884 (1.226-2.896)). Use of warfarin (HR 0.506 (0.304-0.842)) and statins (HR 0.585 (0.435-0.785)) were associated with significantly lower mortality. CONCLUSIONS In our Asian population presenting with HFpEF, two-year mortality was 26.6%. Ethnicity did not predict mortality. Older age, prior myocardial infarction, prior stroke, smoking, and higher creatinine levels were found to be significant predictors of mortality.

Predictors of mortality in acute heart failure: interaction between diabetes and impaired left ventricular ejection fraction.

The aim of this study was to test the hypothesis that diabetes modifies the risk of mortality in acute heart failure patients, especially in patients with impaired LVEF, and that impaired LVEF in turn modifies the risk of mortality in diabetic patients.

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.