Cardiac C-arm CT is a valuable imaging modality that can provide three-dimensional images of the heart during an interventional procedure. As the technology advances to provide better image quality and faster acquisition times, the potential clinical uses increase. Visualization of myocardial defects could directly impact the guidance, procedure time, and outcome of various interventional procedures. In this work, I developed protocols to optimize low-contrast detectability for cardiac C-arm CT and performed in vivo studies to validate using C-arm CT for imaging myocardial necrosis during a cardiac interventional procedure. Initial in vivo investigations were used to evaluate the contrast injection protocol for ideal timing, dilution, catheter type, and injection location. Additionally, x-ray parameters including filtration, kVp, dose, and collimation were optimized for low-contrast detectability and minimization of artifacts. A 4 sweep x 5 s, ECG-gated imaging protocol using low energy (70-90 kVp) and high dose (1.2 [mu]Gy/projection) optimizes low contrast detectability, while collimation around the heart improves SNR by reducing scatter. Images acquired both in vivo and in a slab phantom show that tight collimation and beam filtration result in improved SNR and a reduction of shading artifacts. Visualization of radiofrequency ablation lesions using contrast enhanced C-arm CT during the procedure provides a direct assessment of adequate lesion formation and may circumvent complications associated with cardiac ablation procedures. An in vivo validation study was completed in 9 swine by comparing lesion dimensions measured in C-arm CT images and pathology specimens. All ablation lesions were visualized and lesion dimensions, as measured on C-arm CT, correlated well with postmortem tissue measurements using triphenyltetrazolium chloride (TTC) staining (mean difference 1D dimensions: 0.09 ± 1.04 mm, area: -0.71 ± 5.86 mm2). C-arm CT visualization of myocardial infarction (MI) in the catheterization lab could furnish early prognostic information for risk stratification as well as provide 3D images for guidance of stem cell or ablation therapies. A porcine model using balloon occlusion in the coronary artery was used to study visualization of acute and subacute MI in 12 swine. Contrast enhanced C-arm CT imaging was performed the day of infarct creation or 4 weeks after infarct creation and the volume of the infarct was compared against pathology to validate the visualization of infarction. Acute MI is best visualized at 1 minute post contrast injection as a region of combined hyper- and hypoenhancement whereas subacute MI appears as a region of hyperenhancement with peak contrast enhancement at 5 minutes post contrast injection. C-arm CT infarct volumes compared well with TTC staining (mean difference acute: -0.5 cm3, subacute: -0.7cm3). In conclusion, cardiac C-arm CT with contrast and imaging protocols optimized for low-contrast detectability has been established as a consistent and reliable technique for imaging myocardial necrotic tissue in the interventional suite.