Screening for earlY Heart Failure Diagnosis and Management in Primary Care or at HOme Using Natriuretic Peptides and echocardiographY SYMPHONY-HF

Study Overview
=================
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.

Official Title
-----------------
Screening for earlY Heart Failure Diagnosis and Management in Primary Care or at HOme Using Natriuretic Peptides and echocardiographY

Conditions
-----------------
Heart Failure, Cardiovascular Diseases

Intervention / Treatment
-----------------
* Diagnostic Test: NT-proBNP


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female ≥40 years of age Informed consent Two or more of the following risk factors for heart failure: 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]) An established diagnosis of diabetes (type 1 or type 2) Persistent or permanent atrial fibrillation (not paroxysmal atrial fibrillation) Previous ischemic or embolic stroke Peripheral arterial disease (previous surgical or percutaneous revascularisation or a documented stenosis greater than 50% of a major peripheral arterial vessel). 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). Regular loop diuretic use (any dose at any dosing interval) for >30 days. 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

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Routine care arm<br>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. | |
| Experimental: Investigational arm<br>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. | Diagnostic Test: NT-proBNP<br>* 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).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnosis of heart failure within 6 months |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnosis of HFrEF within 6 months |  | 6 months | 
| People diagnosed with HFrEF receiving GDMT within 6 months |  | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Screening, Biomarker, NT-proBNP, Echocardiography, Community, Registry