Heart Failure, Heart Failure and Reduced Ejection Fraction
Conditions
Keywords
LVEF, HFrEF, HFrecEF, Perfusion Imaging, Adenosine, Cardiac Magnetic Resonance Imaging
Brief summary
Background: Heart failure with reduced ejection fraction (HFrEF) is a heterogeneous condition with variable potential for left ventricular ejection fraction (LVEF) recovery. While LVEF improvement and reverse remodeling predict better outcomes, the determinants that predict left ventricular recovery remain poorly understood. An expert panel of the Journal of American College of Cardiology highlighted the need for improved HFrEF phenotyping to clarify recovery patterns and support personalized management and risk stratification. Methods: PRIMA-HF is a prospective prediction study designed to determine whether baseline cardiac multimodality imaging can predict LVEF recovery in patients with de novo HFrEF (n=180). The imaging protocol includes cardiac magnetic resonance (CMR), coronary computed tomography and \[¹⁵O\]H₂O positron emission tomography (\[¹⁵O\]H₂O-PET) and echocardiography. Patients will also undergo a six-minute walk test, blood volume measurement, and blood sampling. The primary outcome is the change in LVEF from baseline to approx. after 3-12 months (or after full optitration in GDMT), assessed by CMR. In 60 patients from the PRIMA-HF cohort, the randomized, double-blind study High Dose Adenosine During Perfusion Imaging in Heart Failure (HAI-HF) will be conducted. HAI-HF evaluates whether high-dose adenosine (210 µg/kg/min) versus standard-dose (140 µg/kg/min) during \[¹⁵O\]H₂O-PET changes the stress myocardial blood flow, which is the primary endpoint. Aim: The PRIMA-HF study comprehensively characterizes patients with newly diagnosed HFrEF through multimodality imaging and systematically assesses change in LVEF using CMR. The study's deep phenotyping approach integrates clinical, imaging, biomarker, and functional data to capture disease heterogeneity, rather than relying on traditional measures such as LVEF or symptom class. This enables the identification of distinct patient subgroups with shared pathophysiological mechanisms. The HAI-HF trial examines whether higher adenosine doses improve \[¹⁵O\]H₂O-PET perfusion imaging in HFrEF. Together, the studies will advance understanding of myocardial recovery, improve perfusion assessment, and support development of a predictive model for HFrEF prognosis.
Interventions
DIAGNOSTIC_TESTHAI-HF: Adenosine Stress [¹⁵O]H₂O PET Imaging
HAI-HF: Patients will be randomized in a 1:1 ratio to one of two dosing sequences: high-dose followed by low-dose adenosine, or low-dose followed by high-dose adenosine.
DRUGTwo different doses of adenosine
Testing if high dose adenosine (210 ug/kg/min) during perfusion imaging results in a higher myocardial blood flow compared to standard dose (140 ug/kg/min) in patients with HFrEF
Sponsors
Gødstrup Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Capable and has provided written informed consent * LVEF ≤ 40% by echocardiography in connection with hospitalization for heart failure or in connection with outpatient evaluation for heart failure
Exclusion criteria
* Previous diagnosis of heart failure * Unable to understand the patient information * Pregnancy, as the study involves ionizing radiation. * Current severe valvular disease (as defined by the Danish national treatment guidelines on cardio.dk) * Atrial fibrillation with a heart rate \> 130 beats per minute during the inclusion echocardiography * Cardiac surgery within 6 months prior to inclusion * Acute exacerbation of existing chronic obstructive pulmonary disease * Severe asthma or chronic obstructive pulmonary disease with FEV1 \< 1L * any contraindication for adenosine stress testing * Severe renal failure \< 15 mL/min/1.73m² or dialysis * Advanced liver disease (Child-Pugh class C) * Endocarditis at inclusion/baseline * Isolated right-sided heart failure * Malignant disease treated with chemotherapy or radiotherapy, or expected life expectancy under 1 year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PRIMA-HF: Left ventricular ejection fraction (LVEF) | PRIMA-HF: Baseline through study completion, an average of 3 months | Change in LVEF (continuous variable, absolute change in LVEF in percent points) |
| HAI-HF: Stress Myocardial Blood Flow (MBF) | Baseline and periprocedural | Change in stress MBF (continuous variable, ml/min/g) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PRIMA-HF: Kansas City Cardiomyopathy Questionaire (KCCQ-12) | Baseline through study completion, an average of 3 months | Change in Kansas City Cardiomyopathy Questionnaire (KCCQ-12) (points, continuous data) |
| PRIMA-HF: 6 minutes-walk-test | Baseline through study completion, an average of 3 months | Change in 6MWT distance (meters, continuous data) |
Other
| Measure | Time frame | Description |
|---|---|---|
| PRIMA-HF: Blood volume | Baseline through study completion, an average of 3 months | Change in blodvolume (L, continuous data) |
| PRIMA-HF: NT-Pro-BNP | Baseline through study completion, an average of 3 months | Change in NT-Pro-BNP (pg/mL or pmol/L, continuous data) |
Countries
Denmark
Outcome results
None listed