Cardiovascular Diseases, Heart Failure
Conditions
Keywords
Screening, Biomarker, NT-proBNP, Echocardiography, Community, Registry
Brief summary
This is an international prospective, multicentre, unblinded, randomised-controlled trial. The primary aim is to assess a targeted screening strategy to detect undiagnosed heart failure in high-risk patients.
Detailed description
The primary aim is to assess a targeted screening strategy to detect undiagnosed heart failure (HF) in high-risk patients. Participants will be recruited from 5-countries (Denmark, Canada, United States of America, Sweden and Scotland). Individual patient data from similar national randomised controlled trials that are independently powered for different efficacy endpoints will be pooled, harmonised and analysed. After agreeing to consent, patients will be randomised to one of two arms: Routine care arm - patients in this arm will undergo routine care. They will be managed and followed up as per routine clinical care. They will be remotely monitored for HF events by follow up through electronic records and routinely collected data. OR Investigational arm - patients in this arm will have a blood sample performed for measurement of N-terminal prohormone of B-type natriuretic peptide (NT-proBNP). Patients with an elevated Roche NT-proBNP (≥125 pg/mL) will undergo a transthoracic echocardiogram, clinical examination for signs of HF, HF symptom assessment, an ECG). Patients will undergo echocardiography with a CE-marked, FDA-approved handheld point of care (POC) EchoNous echocardiogram device in all countries. The US2.ai algorithm (which is also CE-marked and FDA-approved) will generate an AI-automated echocardiogram report. In Scotland all patients will also undergo a conventional echocardiogram. Patients who are classified as having heart failure (Heart failure with reduced ejection fraction \[HFrEF\], Heart failure with moderately reduced ejection fraction \[HFmrEF\] and Heart failure with preserved ejection fraction \[HFpEF\]) will be referred for appropriate follow up. In all countries when a handheld echocardiogram reported by AI-automated software does not provide diagnostic images a conventional echocardiogram will be undertaken.
Interventions
DIAGNOSTIC_TESTNT-proBNP
Patients will undergo an NT-proBNP which will guide their future involvement within the study. Patients with an NT-proBNP of ≥125 pg/mL will undergo transthoracic echocardiogram along with a clinical assessment - any diagnosis of HF will result in patients undergoing referral for initiation of guideline directed medical therapy (for HF).
Sponsors
University of Glasgow
National Heart Centre Singapore
Karolinska University Hospital
Uppsala University
Montreal Heart Institute
Rigshospitalet, Denmark
University of British Columbia
The Cleveland Clinic
Université de Montréal
AstraZeneca
Roche Pharma AG
Us2.ai
NHS Greater Glasgow and Clyde
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
After agreeing to consent, patients will be randomised 1:1 to one of two arms; a Routine care arm in which patients will undergo routine care or a 2. Investigational arm - patients in this arm will have a blood sample performed for measurement of N-terminal prohormone of B-type natriuretic peptide (NT-proBNP). Patients with an elevated Roche NT-proBNP (≥125 pg/mL) will undergo a transthoracic echocardiogram, clinical examination for signs of HF, HF symptom assessment, an ECG). Patients will undergo echocardiography with a CE-marked, FDA-approved handheld point of care (POC) EchoNous echocardiogram device in all countries. The US2.ai algorithm (which is also CE-marked and FDA-approved) will generate an AI-automated echocardiogram report. In Scotland all patients will also undergo a conventional echocardiogram. Patients who are classified as having heart failure (HFrEF, HFmrEF and HFpEF) will be referred for appropriate follow up.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female ≥40 years of age * Informed consent * Two or more of the following risk factors for heart failure: 1. Coronary artery disease (either a previous documented type 1 myocardial infarction or coronary artery bypass grafting or percutaneous coronary intervention or documented stenosis of an epicardial coronary artery \[50% left main stem or \>70% left anterior descending, circumflex or right coronary artery\]) 2. An established diagnosis of diabetes (type 1 or type 2) 3. Persistent or permanent atrial fibrillation (not paroxysmal atrial fibrillation) 4. Previous ischemic or embolic stroke 5. Peripheral arterial disease (previous surgical or percutaneous revascularisation or a documented stenosis greater than 50% of a major peripheral arterial vessel). 6. Chronic kidney disease (defined as an estimated glomerular filtration rate \<60mL/min/1.73m2 or eGFR 60-90mL/min/1.73m2 and UACR \>300mg/g). 7. Regular loop diuretic use (any dose at any dosing interval) for \>30 days. 8. COPD (evidenced by one of the following: PFTs showing airway obstruction, diagnosis by respiratory physician, CT scan reporting presence of emphysema or treatment with national guideline advocated COPD therapy).
Exclusion criteria
* Inability to give informed consent e.g., due to significant cognitive impairment * Previous documented diagnosis of heart failure * Current renal replacement therapy * Anyone who, in the investigators' opinion, is not suitable to participate in the trial for other reasons e.g., a diagnosis which may compromise survival over the study period
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Diagnosis of heart failure within 6 months | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| People diagnosed with HFrEF receiving GDMT within 6 months | 6 months |
| Diagnosis of HFrEF within 6 months | 6 months |
Other
| Measure | Time frame |
|---|---|
| Diagnosis of HFpEF within 6 months | 6 months |
| People diagnosed with HFmrEF and HFpEF receiving SGLT2i therapy within 6 months | 6 months |
| Diagnosis of asymptomatic left ventricular dysfunction (LVEF≤40%) within 6 months | 6 months |
| Time to first heart failure hospitalisation at 1 year | 1 year |
| Time to first heart failure hospitalisation at 2 years | 2 years |
| Time to first heart failure hospitalisation at 5 years | 5 years |
| All-cause mortality at 1 year | 1 year |
| All-cause mortality at 2 years | 2 years |
| All-cause mortality at 5 years | 5 years |
| Time to first occurence of any components of the following clinical composite 1) heart failure hospitalisation 2) all-cause mortality at 1 year | 1 year |
| Time to first occurence of any components of the following clinical composite 1) heart failure hospitalisation 2) all-cause mortality at 2 years | 2 years |
| Time to first occurence of any components of the following clinical composite 1) heart failure hospitalisation 2) all-cause mortality at 5 years | 5 years |
| The incremental cost-effectiveness ratio (ICER) will be expressed as incremental costs/life-year gained | 5 years |
| The number of patients in the NT-proBNP/echocardiography group with echocardiographic features of potential amyloid as assessed by the US2.ai algorithm report conclusion of amyloid to be considered | 6 months |
| Diagnosis of HFmrEF within 6 months | 6 months |
Countries
Canada, Denmark, Sweden, United Kingdom, United States
Contacts
Primary ContactMark C Petrie, MbChB
Backup ContactKieran F Docherty, MbChB
Outcome results
None listed