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

Официальное название

PRIMA-HF PRedicting Recovery of Left Ventricular Function With Multimodality Cardiac IMAging in Patients With de Novo Heart Failure HAI-HF: High-Dose Adenosine During Perfusion Imaging in Heart Failure: Rationale and Design of the HAI-HF Trial

Обзор

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.

Вмешательства

• Диагностический тест 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.
• Препарат 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

Первичные конечные точки

• PRIMA-HF: Left ventricular ejection fraction (LVEF) [Срок оценки: PRIMA-HF: Baseline through study completion, an average of 3 months]
• HAI-HF: Stress Myocardial Blood Flow (MBF) [Срок оценки: Baseline and periprocedural]

Вторичные конечные точки (2)

• PRIMA-HF: Kansas City Cardiomyopathy Questionaire (KCCQ-12) [Срок оценки: Baseline through study completion, an average of 3 months]
• PRIMA-HF: 6 minutes-walk-test [Срок оценки: Baseline through study completion, an average of 3 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Диагностика

Центры проведения

Дания · 1 центр

• University Clinic of Cardiovascular Reseach — Herning

Публикации

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• Kim IC, Yoo BS. Multidimensional Approach of Heart Failure Diagnosis and Prognostication Utilizing Cardiac Imaging with Biomarkers. Diagnostics (Basel). 2022 Jun 1;12(6):1366. doi: 10.3390/diagnostics12061366. PMID 35741176
• Wilcox J, Yancy CW. Stopping medication for heart failure with improved ejection fraction. Lancet. 2019 Jan 5;393(10166):8-10. doi: 10.1016/S0140-6736(18)32825-3. Epub 2018 Nov 11. No abstract available. PMID 30429051
• Wilcox JE, Fang JC, Margulies KB, Mann DL. Heart Failure With Recovered Left Ventricular Ejection Fraction: JACC Scientific Expert Panel. J Am Coll Cardiol. 2020 Aug 11;76(6):719-734. doi: 10.1016/j.jacc.2020.05.075. PMID 32762907
• Postnov DD, Tuchin VV, Sosnovtseva O. Estimation of vessel diameter and blood flow dynamics from laser speckle images. Biomed Opt Express. 2016 Jun 22;7(7):2759-68. doi: 10.1364/BOE.7.002759. eCollection 2016 Jul 1. PMID 27446704
• Borges JP, Lopes GO, Verri V, Coelho MP, Nascimento PM, Kopiler DA, Tibirica E. A novel effective method for the assessment of microvascular function in male patients with coronary artery disease: a pilot study using laser speckle contrast imaging. Braz J Med Biol Res. 2016 Sep 1;49(10):e5541. doi: 10.1590/1414-431X20165541. PMID 27599202
• Strobeck JE, Feldschuh J, Miller WL. Heart Failure Outcomes With Volume-Guided Management. JACC Heart Fail. 2018 Nov;6(11):940-948. doi: 10.1016/j.jchf.2018.06.017. Epub 2018 Oct 10. PMID 30316941
• Bello D, Shah DJ, Farah GM, Di Luzio S, Parker M, Johnson MR, Cotts WG, Klocke FJ, Bonow RO, Judd RM, Gheorghiade M, Kim RJ. Gadolinium cardiovascular magnetic resonance predicts reversible myocardial dysfunction and remodeling in patients with heart failure undergoing beta-blocker therapy. Circulation. 2003 Oct 21;108(16):1945-53. doi: 10.1161/01.CIR.0000095029.57483.60. Epub 2003 Oct 13. PMID 14557364

Идентификаторы

NCT: NCT07243119 · 1-10-72-126-25

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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