BACKGROUND: Epidemiological studies have consistently associated cytomegalovirus (CMV) seropositivity with adverse cardiovascular outcomes. However, the mechanisms by which cytomegalovirus infection impacts pathophysiology in the heart remain poorly understood. In this study, we sought to dissect how latent murine cytomegalovirus infection impacts cardiac immune cell dynamics at steady-state and during postmyocardial infarction (MI) repair. METHODS: Experimental MI studies were conducted in C57BL/6J mice previously infected with murine cytomegalovirus. In situ inflammatory responses were characterized by spectral flow cytometry, bulk and single-cell RNA/T-cell receptor (TCR) sequencing, whereas cardiac function was monitored by echocardiography and cardiac magnetic resonance imaging. Moreover, we retrospectively assessed the cytomegalovirus serostatus and associated T-cell expansions in a well-characterized patient cohort with longitudinal cardiac magnetic resonance imaging data available and performed bulk TCR sequencing on peripheral blood and myocardial samples to identify cytomegalovirus-specific TCRs. RESULTS: Our findings show that exposure to murine cytomegalovirus induces long-term changes in the cardiac transcriptional profile and alterations in various cardiac-resident immune cell populations, including the establishment of virus-specific memory CD8 ⁺ T-cell residency. Compared with infarcted controls, mice previously exposed to murine cytomegalovirus exhibited stronger inflammatory responses marked by increased CD8 ⁺ T-cell infiltration and worsened cardiac function following MI. These observations in mice were supported by data from patients with cytomegalovirus seropositive MI, who harbored cytomegalovirus-responsive T cells in the heart. CONCLUSIONS: Our findings demonstrate that latent cytomegalovirus infection leads to long-term changes in the cardiac microenvironment, which ultimately impair post-MI healing outcomes.

Purpose: Cardiac inflammation plays a key role in many diseases. However, its underlying mechanisms and progression remain poorly understood. Using an ultra‐high field (UHF) may increase the sensitivity of MRI of inflammatory processes with ¹⁹ F‐labeled immune cells. The high Larmor frequency of ¹⁹ F (∼95% of that for ¹ H‐nuclei) leads to similar technical hurdles in acquiring MR images at UHF that originate from the heterogeneity of B ₁ ⁺ . We aimed to develop a system of transmit/receive (Tx/Rx) arrays exploiting parallel transmit (pTX) technology for B ₁ ⁺ ‐shimming to acquire a combination of high‐quality anatomical ¹ H MR‐images of a pig heart and ¹⁹ F images of labeled immune cells at 7T. Method: The 16‐element twin‐arrays for ¹ H and ¹⁹ F nuclei were designed using electromagnetic simulations with a focus on optimal B ₁ ‐shimming and g‐factor in the region of the pig heart. pTX support allows for the subject‐specific B ₁ ‐shimming for ¹ H cardiac MRI and transfer of settings for the B ₁ ‐shimming to the ¹⁹ F twin‐array. Results: The twin‐array system was implemented and tested in a pig‐thorax‐‐shaped phantom, in‐vivo in a myocardial infarction pig model, and in an excised heart. A transfer of static B ₁ + shimming setting between the ¹ H to ¹⁹ F arrays was demonstrated. The parallel imaging acceleration of up to a factor 4 was possible with a g‐factor <1.3 for both arrays. The 7T MRI of ¹⁹ F‐labeled immune cells in the heart of the pig was demonstrated both in‐vivo and ex‐vivo. Conclusion: The 7T MRI of perfluorocarbon‐labeled immune cells in a large‐animal myocardial infarction model becomes feasible using a novel dedicated twin‐arrays system.