Hyperpolarized MRSI in Ischemic Heart Disease: A Metabolic Investigation of the Heart Muscle

Hyperpolarized MRSI in Ischemic Heart Disease: Metabolic Profiling of the Myocardium

This study aims to investigate the potential of using hyperpolarized [1-13C]-pyruvate magnetic resonance imaging (MRI) to assess metabolic alterations in patients with ischemic heart disease (IHD). Altered myocardial metabolism is recognized as a crucial factor in heart failure and IHD, and modulating cardiac metabolism offers a new approach to treatment. However, current diagnostic modalities use ionizing radiation and have shown limited prognostic value.

Hyperpolarization through dynamic nuclear polarization (DNP) enables highly sensitive in vivo detection of metabolic processes. Hyperpolarized [1-13C]-pyruvate allows visualization of glycolysis-related metabolism, providing insights into the breakdown of glucose and its derivatives. By using this technique, the study aims to differentiate viable from non-viable myocardium in patients with IHD.

The objectives include implementing hyperpolarized [1-13C]-pyruvate cardiac MRI to image metabolic flux in the human heart and investigating the potential of this method to distinguish viable from non-viable myocardium in patients with IHD. The study endpoints involve assessing metabolic flux through the pyruvate dehydrogenase complex (PDC) and analyzing ratios of different metabolites, which can indicate the extent of pyruvate oxidation and lactate production.

A cross-sectional study design involving patients with CHF and ischemic heart disease will be used. Patients will undergo hyperpolarized [1-13C]-pyruvate MRI, PET imaging, late gadolinium enhancement (LGE) MRI, and cardiac magnetic resonance imaging (CMR). The study will compare [1-13C]-pyruvate MRI findings with PET results, allowing for a correlation between metabolic data and traditional imaging techniques. This innovative approach could provide valuable insights into the metabolic changes associated with ischemic heart disease

Inclusion Criteria:

• Chronic heart failure
• >18 years of age
• Left ventricular Ejection Fraction (LVEF) of 10 - 60 %
• Adequate hematologic and organ function.
• Women who are not postmenopausal or surgically sterile must have a negative serum or urine pregnancy test performed at time of inclusion in the study.
• Safe and highly effective contraception must be used throughout the study meaning either hormonal anti-conception or an anti-fertility intrauterine device. If the partner is non fertile or the patient has no sexual activities, this is also accepted.
• Non-insulin dependent Diabetes mellitus is allowed
• Danish speaking
• Able and willing to comply after informed consent
• Ischemic heart disease and referral to viability testing at the Department of Clinical Physiology and Nuclear Medicine at Aarhus University Hospital.

Exclusion Criteria:

• Not able or willing to receive heart failure therapy
• Patients not willing to participate
• Uncontrolled serious medical condition, such as uncontrolled heart disease, uncontrolled diabetes, intestinal obstruction, uncontrolled hypertension, or recent cerebral ischemia
• Estimated Glomerular Filtration Rate (eGFR) <30 mL/min
• Insulin dependent Diabetes Mellitus
• Intolerance to Pyruvate