In this study the investigators propose to detect early mitochondrial metabolic changes in the heart in patients with a positive genotype and phenotype for HCM using a novel hyperpolarized [1-13C]pyruvate MRI methodology. Carbon-13 is a stable isotope (not radioactive) that makes up approximately 1.1% of all natural carbon. Carbon-13 has a non-zero spin quantum number that allows the investigation of carbon containing substances using magnetic resonance. However, compared with other analytical methods, carbon-13 magnetic resonance has been limited by an intrinsically low sensitivity [2}.~Recent experimental studies suggest that altered energy substrate metabolism may precede structural changes in myocardial hypertrophy. A better understanding of the myocardial metabolic changes in HCM is important, as the elucidation of such changes may precede the clinical development of myocardial fibrosis and malignant arrhythmias. Hyperpolarized [1-13C]pyruvate and its cellular metabolic flux can be assessed with a more than 10,000-fold higher sensitivity compared to traditional methods. The aim of this pilot study is to test the hypothesis that patients with HCM present focal alterations in myocardial hyperpolarized [1-13C]pyruvate flux.~To achieve this aim the investigators will assess myocardial metabolic changes in HCM subjects with a positive HCM genotype and phenotype (n=5) and in healthy control subjects (n=5) who are matched for age, sex, and Body Mass Index (BMI). Total target enrollment will be set at 15 subjects to allow for attrition and screen failures.~Cardiac function and structure will be evaluated with MRI (proton imaging) before and after contrast administration. Then myocardial metabolism will be assessed utilizing MRS (carbon spectroscopy) before and after intravenous injection with hyperpolarized [1-13C]pyruvate. The study agent, hyperpolarized [1-13C]pyruvate, will be administered under a Food and Drug Administration (FDA) Investigational New Drug (IND), currently in review process, PI Dr. Craig Malloy.~Human preliminary data are essential to secure larger scale funding required for clinical studies. The identification of mitochondrial metabolic changes preceding replacement fibrosis and malignant arrhythmias may generate a paradigm shift to early detection and more targeted treatment of HCM with potentially improved clinical outcomes. Cardiac focused applications at the Advanced Imaging Research Center, genetic disease diagnosis at the Eugene McDermott Center for Human Genetics and the development of a dedicated HCM Clinic at the UT Southwestern Medical Center offer today a unique opportunity to lead globally the translational scientific efforts in this field.
In this study the investigators propose to detect early mitochondrial metabolic changes in the heart in patients with a positive genotype and phenotype for Hypertrophic Cardiomyopathy (HCM) using a novel hyperpolarized [1-13C]pyruvate Magnetic Resonance Imaging (MRI) methodology.