Gill, Nathan

Background: The prevalence of cardiac implantable electronic devices (CIED) is increasing, with over 300,000 new implants annually in the U.S. Stress cardiac magnetic resonance (CMR) has proven as a powerful modality for myocardial characterization, enabling accurate diagnosis of different cardiac conditions. In patients without devices, CMR findings have also demonstrated prognostic value for major adverse cardiovascular events (MACE) and guide clinical decision-making. However, its use in CIED patients has historically been limited due to safety and image quality concerns. Hypothesis: We aimed to evaluate the prognostic value of CMR imaging using wideband sequences in CIED patients. Methods: CIED patients referred for clinical CMR were included prospectively and retrospectively between January 2020 and February 2025. All patients underwent a stress CMR protocol, which included cine, wideband late gadolinium enhancement (LGE), wideband T1 mapping, and wideband stress/rest perfusion imaging. Clinical follow-up is ongoing. The primary endpoint was the occurrence of MACE, defined as the composite of myocardial infarction, heart failure hospitalization, implantable cardioverter defibrillator (ICD) therapy, cardiac death, revascularization, or heart transplant. Results: A total of 89 patients were included (median age 69.0 [58.0–75.5] years; 62.9% male). Device types included pacemakers (33.7%), ICDs (48.3%), and cardiac resynchronization therapy devices (16.9%). Over a median of follow-up of 613 days [355-991], 21 patients experienced a MACE. In unadjusted models, higher left ventricular ejection fraction (LVEF) (per 5%) was significantly associated with a lower risk of MACE (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.65–0.95; p=0.016), as was higher stress myocardial blood flow (MBF) (per 0.25 mL/g/min increase: OR 0.78, 95% CI 0.60–0.98; p=0.05). In contrast, greater LV myocardial mass (per 10 g) was significantly associated with a higher risk of MACE (OR 1.27, 95% CI 1.08–1.52; p = 0.006), figure 1. Conclusion: The use of wideband sequences enabled the assessment of prognostic imaging value in CIED patients. LVEF remains a strong and consistent predictor of MACE in this population and LV mass was significantly associated with higher rates of MACE reflecting the influence of underlying cardiomyopathy. While stress perfusion CMR imaging showed promising trends, further studies with longer follow-up are needed to clarify its prognostic value in this population.

Abstract The TDP-43 type C pathological form of frontotemporal lobar degeneration is characterized by the presence of immunoreactive TDP-43 short and long dystrophic neurites, neuronal cytoplasmic inclusions, neuronal loss and gliosis and the absence of neuronal intranuclear inclusions. Frontotemporal lobar degeneration-TDP-type C cases are commonly associated with the semantic variant of primary progressive aphasia or behavioural variant frontotemporal dementia. Here, we provide detailed characterization of regional distributions of pathological TDP-43 and neuronal loss and gliosis in cortical and subcortical regions in 10 TDP-type C cases and investigate the relationship between inclusions and neuronal loss and gliosis. Specimens were obtained from the first 10 TDP-type C cases accessioned from the Northwestern Alzheimer’s Disease Research Center (semantic variant of primary progressive aphasia, n = 7; behavioural variant frontotemporal dementia, n = 3). A total of 42 cortical (majority bilateral) and subcortical regions were immunostained with a phosphorylated TDP-43 antibody and/or stained with haematoxylin–eosin. Regions were evaluated for atrophy, and for long dystrophic neurites, short dystrophic neurites, neuronal cytoplasmic inclusions, and neuronal loss and gliosis using a semiquantitative 5-point scale. We calculated a ‘neuron-to-inclusion’ score (TDP-type C mean score – neuronal loss and gliosis mean score) for each region per case to assess the relationship between TDP-type C inclusions and neuronal loss and gliosis. Primary progressive aphasia cases demonstrated leftward asymmetry of cortical atrophy consistent with the aphasic phenotype. We also observed abundant inclusions and neurodegeneration in both cortical and subcortical regions, with certain subcortical regions emerging as particularly vulnerable to dystrophic neurites (e.g. amygdala, caudate and putamen). Interestingly, linear mixed models showed that regions with lowest TDP-type C pathology had high neuronal dropout, and conversely, regions with abundant pathology displayed relatively preserved neuronal densities (P < 0.05). This inverse relationship between the extent of TDP-positive inclusions and neuronal loss may reflect a process whereby inclusions disappear as their associated neurons are lost. Together, these findings offer insight into the putative substrates of neurodegeneration in unique dementia syndromes.