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While new studies emphasize that patients with a CAC greater than or equal to 1000 be considered a distinct patient group, a CAC of 0 has additionally emerged to be a reliable negative risk factor, identifying patients at low risk of both CVD and non-CVD mortality. © RSNA, 2020. To implement, validate, and apply a self-gated free-running whole-heart five-dimensional (5D) flow MRI framework to evaluate respiration-driven effects on three-dimensional (3D) hemodynamics in a clinical setting. In this prospective study, a free-running five