Heart Failure Clinical Studies

This theme is led primarily by Associate Professor Carolyn S.P. Lam.

 

OBSERVATIONAL STUDIES

1. ASIAN-HF Study

Aims: We aim to determine mortality and morbidity in Asian patients under clinical management for heart failure (HF). Specifically, we will define the incidence of, and risk factors for, sudden cardiac death, as well as the sociocultural factors influencing therapeutic choices in these patients.

Methods: This is a prospective observational multinational Asian registry of 5000 patients with symptomatic HF (Stage C) and left ventricular systolic dysfunction (ejection fraction < 40%) involving 40 centres across 10 Asian regions (Korea, Thailand, Indonesia, Philippines, India, Japan, Malaysia, Hong Kong, China, and Singapore). Data collection includes demographic variables, clinical symptoms, functional status, date of HF diagnosis and prior cardiovascular investigations, clinical risk factors, lifestyle factors, socioeconomic status, and survey of cultural beliefs, health practices and attitudes towards device therapy. Centre-level characteristics (caseload, referral pattern, specialization, infrastructure) are also obtained. Patients uniformly undergo standard 12-lead electrocardiography and transthoracic echocardiography at baseline, and are followed over 3 years for outcomes of death or hospitalization. The mode of death and cause of hospitalization are adjudicated by a central event adjudication committee using pre-specified criteria.

Conclusion: By providing prospective data regarding the demographics, risk factors, and outcomes of Asian patients under treatment for HF, the ASIAN-HF registry is expected to advance fundamental understanding of the burden and predictors of death and hospitalization among these patients. The knowledge gained will be important for guiding resource allocation and planning preventive strategies to address the unmet and growing clinical needs of patients with cardiovascular disease in Asia.


2. Singapore Heart Failure Outcomes and Phenotypes Study

Heart failure (HF) with preserved ejection fraction (HF-PEF) is a major public health problem. While studies from Western populations suggest that the prevalence and outcomes for HF-PEF are similar to that of HF with low ejection fraction (HF-lowEF), results vary widely and virtually no data exists in Asian populations. The continued lack of proven therapies in HF-PEF underscores the existing knowledge gaps regarding key pathophysiologic characteristics of this syndrome. Accordingly, our long-term goal is to advance fundamental understanding of the pathophysiology and epidemiology of HF-PEF, allowing therapeutic targets to be identified for its prevention and treatment.

Specific Aims

1. Determine the overall prevalence and inter-ethnic differences in prevalence of HF-PEF within the population presenting with decompensated HF. We hypothesize that HF-PEF accounts for 50% of presentations and differs by ethnicity due to ethnic-specific differences in underlying substrates (including hypertension and diabetes) for HF.

2. Determine the clinical outcome of HF-PEF compared to HF-lowEF. We hypothesize that HF-PEF patients have lower mortality and rehospitalisation rates compared to HF-lowEF patients.

3. Obtain detailed phenotypic characterization of HF-PEF using state-of-the-art methods, compared to HF-lowEF and age-/sex-matched controls without HF. We hypothesize that important cardiovascular structural and functional differences exist between HF-PEF and HF-lowEF, which are discernible on careful phenotypic characterization by echocardiography, vascular assessment, cardiac magnetic resonance imaging and neurohormonal measurements.

To achieve this, we propose a large, prospective multi-centre longitudinal study of in-/out-patients with a primary diagnosis of HF and age-/sex-matched controls without HF from the general community. All will undergo clinical assessment, comprehensive bio-imaging, neurohormonal profiling and follow-up for all-cause mortality and rehospitalisation at 2 years.


3. PEOPLE Study

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 is 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 Outcome in Patients with Heart Failure with Preserved Left Ventricular Ejection Fraction (PEOPLE Study NZ) are parallel prospective studies using identical protocols to enrol patients with HF across 6 centres 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. Cases (n=2500) are patients hospitalized with a primary diagnosis of HF or attending outpatient clinics for management of HF within 6 months of HF decompensation. Controls (n=1250) are age, gender and race matched community-based adults without HF from Singapore. 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. Sub-studies 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 inter-ethnic differences among patients with HF in the Asia-Oceanic region, and will provide unique insights into the pathophysiology and outcomes for these patients. 

 

4. Clinician Scientist Award (INV)

Heart failure (HF) with preserved ejection fraction (HF-PEF) is a major public health problem. While studies from Western populations suggest that the prevalence and outcomes for HF-PEF are similar to that of HF with low ejection fraction (HF-lowEF), results vary widely and virtually no data exists in Asian populations. The continued lack of proven therapies in HF-PEF underscores the existing knowledge gaps regarding key pathophysiologic characteristics of this syndrome.

Specific Aims

1. Determine the overall prevalence and inter-ethnic differences in prevalence of HF-PEF within the population presenting with decompensated HF. We hypothesize that HF-PEF accounts for 50% of presentations and differs by ethnicity due to ethnic-specific differences in underlying substrates (including hypertension and diabetes) for HF.

2. Determine the clinical outcome of HF-PEF compared to HF-lowEF. We hypothesize that HF-PEF patients have lower mortality and rehospitalisation rates compared to HF-lowEF patients.

3. Obtain detailed phenotypic characterization of HF-PEF using state-of-the-art methods, compared to HF-lowEF and age-/sex-matched controls without HF. We hypothesize that important cardiovascular structural and functional differences exist between HF-PEF and HF-lowEF, which are discernible on careful phenotypic characterization by echocardiography, vascular assessment, cardiac magnetic resonance imaging and neurohormonal measurements.

We propose a large, prospective multi-centre longitudinal study of in-/out-patients with a primary diagnosis of HF and age-/sex-matched controls without HF from the general community. All will undergo clinical assessment, comprehensive bio-imaging, neurohormonal profiling and follow-up for all-cause mortality and rehospitalisation at 2 years. 

This research will provide important information regarding the epidemiology, pathophysiology and outcomes of HF-PEF in multiethnic Singapore, leading to greater understanding of the HF burden in Asians and identification of potential therapeutic targets.

 

5. Genetic Markers In Heart Failure

Aim: to leverage upon human cohort studies conducted by the Cardiovascular Research Institute (CVRI), National University Heart Centre Singapore (NUHCS), the technical and analytical capacity of the Genome Institute of Singapore together with special expertise in genetically modified models from the Institute of Medical Biology and the cardiac epigenetics laboratory at Cambridge University, UK, to address the problem of heart failure (HF) a common and lethal chronic illness which constitutes a major clinical and economic burden world-wide. Our multi-disciplinary team will employ methods including rigorous clinical cohort study of 7,000 HF cases with detailed phenotyping, state-of–the-art genomic interrogation and genetically modified animal models to address the genetics underpinning HF, to clarify pathophysiology leading from cardiac injury or stress to decompensated HF, to identify new biomarkers of disease severity and progression and to discover possible new therapies by experiments addressing the hypotheses that: Incident HF with evolution of HF with preserved or reduced ejection fraction and deterioration in cardiac structure/function with clinical progression is associated with distinct patterns of genetic variants; that circulating microRNA profiles will allow prediction of the clinical course towards acute HF from chronic compensated HF and in pre-HF states including post-myocardial infarction (ischaemia, inflammation, myocyte loss) and chronic severe mitral valve regurgitation (volume overload); that in HF and pre-HF specific circulating microRNAs can be identified as candidate therapeutic targets and targetted antagonism of selected microRNAs can ameliorate HF.

 

INTERVENTIONAL TRIALS (INVESTIGATOR-INITIATED)

1.     RESPECT-HF trial of renal denervation in HFPEF

Clinicaltrials.gov ACTRN12613000546752

2.     PRACTISE-ASIA-HF trial of intravenous iron therapy in patients with HF and iron deficiency

Clinicaltrials.gov NCT01922479