Abrogating mitochondrial dynamics in mouse hearts elicits cardiomyopathy which progresses to lethal heart failure. Loss of mitochondrial fusion factors MFN1 and MFN2 drives the development of hypertrophic cardiomyopathy, whilst loss of mitochondrial fission factor DRP1 triggers dilated cardiomyopathy. However, a mechanistic understanding of these distinct aetiologies remains elusive. This thesis used two separate mhy6-driven knockouts of Mfn1/Mfn2 and Drp1 to explore the consequences of abrogated dynamism on calcium cycling in isolated left ventricular cardiomyocytes (LVCs) from mouse. Fusion-deficient LVCs exhibited long-lasting Ca2+ sparks due to slow decay, augmented spark-mediated SR Ca2+ leak and a higher incidence of spontaneous Ca2+ waves (SCWs) compared with controls. During the same window of analyses (3-4 weeks post gene deletion), fusion-deficient LVCs exhibited faster Ca2+ efflux during steady-state contractions when compared with controls, due to the activity of SERCA. Increased SERCA activity may represent a compensatory mechanism to attenuate SR Ca2+ loss and conserve function, but ultimately contribute to pro-arrhythmic SCW genesis. A unifying mechanism which might underlie altered Ca2+ handling in fusion-deficient LVCs is increased RyR open probability (Po). Defective mitochondria which escape mitophagic culling are known to accumulate in this phenotype and emit reactive oxygen species (ROS). This might result in oxidative damage to the RyR macromolecular complex, triggering its destabilisation and hyperactivity. Further investigation will be required to clarify this possibility and determine whether RyR instability plays a causative role in initiating the development of hypertrophic cardiomyopathy in Mfn1/Mfn2 null hearts. Drp1 null heart mass became significantly higher than controls, onset at 4 weeks post gene deletion. Given steady-state calcium handling was overall well-preserved in Drp1 null myocytes at 4 weeks, aberrant calcium cycling is unlikely to drive pathology in this model. Collectively, these results suggest different mechanisms underlie mitochondrial fusion and mitochondrial fission-deficient cardiomyopathies.