Asian Sudden Cardiac Death in Heart Failure(ASIAN-HF) Prospective Observational Study
Conditions: Heart Failure
Sponsor: Carolyn Lam

Asian-HF Synopsis, v1.0, 11Mar2020 
 
CONFIDENTIAL 
 
 
 
Asian Sudden Cardiac Death in Heart Failure 
(ASIAN-HF) registry 
NCT01633398 
Synopsis   

 
 
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Asian-HF Synopsis, v1.0, 11Mar2020 
 
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1. BACKGROUND 
Heart failure (HF) is a major public health problem worldwide. The World Health Organization 
has projected that the largest increases in cardiovascular disease worldwide are occurring in 
Asia, due to rapidly increasing rates of smoking, obesity, dyslipidaemia, and diabetes among 
Asians. Thus the burden of HF is expected to reach epidemic proportions in Asia.  
Yet in sharp contrast to the wealth of data regarding HF in Western nations, epidemiological 
data are scarce in Asian patients with HF. The limited available evidence suggests that there are 
important ethnic-related differences specific to this region, and a large treatment gap exists with 
regards to proven therapies that may contribute to the high mortality and morbidity rates of HF 
in Asia. The lack of data regarding the mortality burden of HF in Asians has contributed to 
underuse of potentially life-saving therapies. Sudden cardiac death (SCD) accounts for ~50% 
of deaths in HF according to Western statistics, with risk of death increasing particularly with 
LVEF<40%. The prophylactic implantation of a defibrillator in at-risk patients with reduced 
LVEF has been shown to reduce SCD and, therefore, has become standard practice in Western 
nations. However, in Asia there is resistance to adoption of similar preventive measures and 
continued controversy regarding the risk of SCD among Asians.  
Given the public health importance of HF, the epidemic of cardiovascular disease in Asia, and 
the availability of potentially lifesaving drugs and devices, but ill-defined barriers to their 
application in Asians, there is an urgent need to fill the knowledge gaps regarding the mortality 
burden of HF, as well as to understand the barriers to preventive drug and device therapy, among 
Asian patients with HF. Such knowledge is critical to define the unmet clinical needs among 
Asian patients with HF, and to guide clinical decisions as well as healthcare resource planning 
to meet these needs. The Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry is 
being initiated to meet these manifest needs. This is a fundamental step towards the long-term 
goal of improving outcomes among the large and growing population of patients with HF in 
Asia. 
 
2. AIMS AND OBJECTIVES OF THE ASIAN-HF STUDY 
The Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry is the first prospective 
multinational Asian registry of patients with symptomatic HF (stage C) initiated towards 
determining the burden of morbidity and mortality in Asian patients. HF patients at least 18 
years old were recruited from 46 medical centres across 11 Asian regions. Data on 
demographics, previous medical history, clinical symptoms, functional status, standard 12-lead 
electrocardiography and transthoracic echocardiography were collected.  
In the HFrEF population, the specific objectives included: 
I. 
The primary objective of this study is to determine the incidence of sudden 
cardiac death (SCD) in Asian patients diagnosed with HF and followed in 
representative Asian cardiovascular centres.  
II. 
To determine the incidence of all-cause and cause-specific death and 
hospitalization among Asian patients with HF.  
III. 
To determine the risk factors for SCD, all-cause death, other cause-specific 
death, and hospitalization among Asian patients with HF.  

 
 
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IV. 
To understand the socio-cultural barriers to device therapy among Asian 
patients. 
V. 
To compare the genetic variants between the two phenotypes of reduced versus 
preserved ejection fraction (HFrEF versus HFpEF).  
In 2013, a protocol amendment included patients with HFpEF (ejection fraction ≥50%). 
 
3. STUDY DESIGN 
This is a prospective, observational, multinational, multicentre Asian registry of patients with 
symptomatic HF (Stage C), including both HFrEF (ejection fraction <40%) and HFpEF 
(ejection fraction ≥50%). The study involved representative medical centres across Asia (China 
and Hong Kong, South Korea, Taiwan, Thailand, Indonesia, Philippines, India, Japan, 
Malaysia, and Singapore). Eligible sites were centres covering a broad spectrum of medical, 
cardiology, and HF specialty units that regularly admit patients with acute HF and follow 
patients with chronic HF in outpatient clinics. Site selection was based on size of the country, 
geographic location of the site within the country, patient population served, HF patient volume, 
and availability of expertise in echocardiography. 
The study was conducted in compliance with the protocol, International Conference on 
Harmonization Good Clinical Practice, E6, and the applicable national regulations in each 
region as to assure that the rights, safety and well-being of the participating study patients are 
protected, in accordance with the ethical principles that have their origin in the Declaration of 
Helsinki (2008).  
Publications from the ASIAN-HF registry are guided by a publication charter and overseen by 
a publications committee. Each outcome event and its cause were adjudicated by a central 
committee using pre-specified criteria. 
 
4. ETHICS 
Independent Ethics Committee (IEC) or Institutional Review Board (IRB) 
At all regions and sites, IEC/IRB approvals were obtained for the study before any study 
activities commenced. All study amendments were submitted to IEC/IRB and approved prior 
to implementation of the amendment activities.  
Ethical Conduct of the Study 
The study was conducted in accordance with the ethical principles that have their origins in the 
Declaration of Helsinki.  
Patient Information and Consent 
Patient informed consent was obtained prior to the commencement of any screening or study 
procedures. The investigator at each site provided full and adequate oral and written information 
about the nature, purpose and available details of possible risks and benefit of the study to each 
potential participant. Patients were also notified that they are free to discontinue from the study 
at any time.  

 
 
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5. STUDY INCLUSION AND EXCLUSION CRITERIA 
Inclusion criteria 
i. Adults (>18 years),  
ii. Symptomatic HF (Stage C HF and any New York Heart Association [NYHA] class 
functional status). Patients should have a current diagnosis of symptomatic HF within 
6 months of an episode of decompensated HF, which either:  
a. resulted in a hospital admission (primary diagnosis) or  
b. was treated in out-patient clinic,  
iii. Left ventricular ejection fraction <40% (HFrEF) or left ventricular ejection fraction 
≥50% (HFpEF) on baseline echocardiography,  
iv. Available for follow-up over 3 years.  
 
Exclusion criteria  
i. Severe valve disease as the primary cause of HF,  
ii. For the HFpEF population: a documented history of reduced ejection fraction (<50%) 
at any time prior to recruitment. In other words, patients with current HFpEF who 
previously had HFrEF will be excluded.  
iii. Life threatening co-morbidity with life expectancy of <1 year,  
iv. Unable or unwilling to give consent,  
v. Concurrent participation in a clinical therapeutic study which requires patient consent.  
 
6. DATA COLLECTION 
Study Schedule and Data Variables 
Patients will be recruited over 2 years and followed up to 3 years, according to the schedule: 
 
Demographic data and clinical data including previous medical, clinical signs/symptoms and 
functional status, and medication use will be collected. Standard 12-lead electrocardiography 
Standard resting 12-lead ECG will be performed at each centre and analysed for rate, rhythm, 
axes, intervals, conduction abnormalities and arrhythmias, and evidence of prior myocardial 
infarction or chamber enlargement. Standard transthoracic echocardiography will also be 
Visit 1:
Baseline
• Medical history
• Questionnaires
• Clinic visit
• ECG
• Echocardiography
Visit 2: 
6 months
• Questionnaires
• Clinic visit
• Vital status & 
outcomes
Visit 3: 
1 year
• Questionnaires
• Clinic visit
• Vital status & 
outcomes
Visit 4/5: 
2/3 years
• Questionnaires
• Clinic visit
• Vital status & 
outcomes

 
 
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performed at each centre according to internationally accepted guidelines and will include 
assessment of LVEF and dimensions, left atrial dimension, LV diastolic function, stroke 
volume, and cardiac output. Questionnaires administered during the study include the Patient 
Profile Questionnaire, Visual Analogue Scale (VAS) for Current Health Perception, Kansas 
City Cardiomyopathy Questionnaire (KCCQ) and the Device Therapy Perception 
Questionnaire.  
 
Outcome determination and adjudication  
The outcomes of interest are all-cause and cause-specific death and hospitalizations, diagnosed 
according to Framingham criteria for the clinical diagnosis of congestive HF. Each outcome 
event and its cause are adjudicated using pre-specified criteria by a central event adjudication 
committee comprising members of the Steering Committee. The data from the case report 
forms, death certificates, hospital discharge summaries will be reviewed independently by 
members of the event adjudication committee and adjudicated based on criteria outlined in the 
event adjudication committee charter. Briefly, all deaths and hospitalizations are classified as 
cardiac or noncardiac, with more specific categories assigned as permitted by the circumstances 
of the clinical event.  
 
7. STUDY RECRUITMENT 
Global Recruitment Summary 
Total study recruitment – 6376 participants  
 
Total HFrEF – 4779 participants 
 
Total HFpEF – 1550 participants 
 
EF criteria not met for HFrEF or HFpEF - 47 participants 
Total genetic samples collected – 1034 samples 
Recruitment by region 
Region  
Total Recruitment
China
488
Hong Kong
104
India
1920
Indonesia
295
Japan
678
Korea
382
Malaysia
638
Philippines
113
Singapore
700
Taiwan
845
Thailand
213
Total 
6376