Objective. 
Photon-counting detectors (PCDs) for CT imaging use energy thresholds to simultaneously acquire projections at multiple energies, making them suitable for spectral imaging and material decomposition. Unfortunately, setting multiple energy thresholds results in noisy analytical reconstructions due to low photon counts in high-energy bins. Iterative reconstruction provides high quality photon-counting CT (PCCT) images but requires enormous computation time for 5D (3D + energy + time) in vivo cardiac imaging. 

Approach. 
We recently introduced UnetU, a deep learning (DL) approach that accurately denoises axial slices from 4D (3D + energy) PCCT reconstructions at various acquisition settings. In this study, we explore UnetU configurations for 5D cardiac PCCT denoising, focusing on singular value decomposition (SVD) modifications along the energy and time dimensions and alternate network architectures such as 3D U-net, FastDVDNet, and Swin Transformer UNet. We compare our networks to multi-energy non-local means (ME NLM), an established PCCT denoising algorithm. 

Main results. 
Our evaluation, using real mouse data and the digital MOBY phantom, revealed that all DL methods were more than 16 times faster than iterative reconstruction. DL denoising with SVD along the energy dimension was most effective, consistently providing low root mean square error and spatio-temporal reduced reference entropic difference, alongside strong qualitative agreement with iterative reconstruction. This superiority was attributed to lower effective rank along the energy dimension than the time dimension in 5D cardiac PCCT reconstructions. ME NLM sometimes outperformed DL with time SVD or time and energy SVD, but lagged behind iterative reconstruction and DL with energy SVD. Among alternate DL architectures with energy SVD, none consistently outperformed UnetU Energy (2D). 

Significance. 
Our study establishes UnetU Energy as an accurate and efficient method for 5D cardiac PCCT denoising, offering a 32-fold speed increase from iterative reconstruction. This advancement sets a new benchmark for DL applications in cardiovascular imaging.