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The complication rates during transcatheter cardiac ablation procedures remain concerning. The transseptal puncture procedure, the relative navigation of catheters to difficult anatomies, and the application of ablation modalities to ensure transmural lesions are all primary areas where therapeutic complications may arise. In my thesis projects, our work targeted these three areas while also specifically considering a means to reduce such complications. Specifically, iatrogenic atrial septal defect formation was investigated by assessing the biomechanical changes of the atrial septum that may occur during transseptal punctures and the further injury the septum may incur during subsequent catheter manipulations. Furthermore, the contact forces required to perforate the atria were characterized in order to determine the boundary force conditions associated with both catheter navigation and ablation energy application. In addition, the biophysical changes manifested during and following the application of ablation modalities, as well as, the parameters that facilitate the development of explosive steam pops were investigated. Finally, the cryothermal tolerances of cardiac tissues were identified to aid in reducing collateral injury and to optimize dose delivery. The insights gained from these translational studies will help define various parameters and boundary conditions that should improve both the safeties and efficacies of clinical cardiac ablation procedures. In addition to characterizing these factors, the direct visualization of such complications provides invaluable insights to engineers as well as clinicians.