PRIMA-HF: Predicting Myocardial Recovery in Heart Failure Using Cardiac Imaging HAI-HF: High Dosing vs. Standard Dosing Adenosine During Myocardial Perfusion in Heart Failure

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.

Conditions

• Heart Failure and Reduced Ejection Fraction
• Heart Failure

Interventions

DIAGNOSTIC_TEST

HAI-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.

DRUG

Two 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 & Collaborators

• Gødstrup Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-12-08

Primary Completion

2029-04-30

Completion

2029-04-30

Countries

• Denmark

Study Locations