P-wave characteristics and histological atrial abnormality.

BACKGROUND: Fibro-fatty transformation is believed to be the leading cause of deteriorated atrial conduction; however, any direct assessment in relation to P-wave characteristics is lacking. We sought to assess P-wave morphology (PWM) and duration (PWD) in relation to histology of the atrial myocardium. OBJECTIVE: Atrial specimens were collected from 11 patients who died from cardiovascular causes (7 men; median age 73 years). METHODS: Tissue samples were taken at the level of superior and inferior PVs, center of posterior left atrial wall, terminal crest (CT) and Bachmann's bundle (BB) for assessment of fibro-fatty tissue extent. Standard 12-lead ECGs in sinus rhythm recorded during hospital stay were used for manual assessment of P-wave. Partial interatrial block (pIAB) was defined as a prolonged (≥ 120 ms) and bimodal P-wave in any lead on 12-lead ECG. RESULTS: The median PWD was 160 (120-200) ms. Fibrosis extent in CT highly correlated to PWD (r=0.914, p<0.001). The combination of fibrosis extent and fatty tissue in BB (16%, range 1%-41%), CT (18%, range 3%-47%) or superior PV (15%, range 6%-24%) correlated to PWD (r=0.627, p=0.039; r=0.795, p=0.003; and r=0.668, p=0.025, respectively). pIAB pattern was observed in 10 subjects; however, it was not associated with either fibrosis or fatty tissue content at any sampling location. CONCLUSIONS: Our findings further support causal association between PWD and the extent of structural abnormalities in the atrial myocardium and the major atrial conduction routes.

Corrigendum to 'quantitative determination of 64Cu-liposome accumulation at inflammatory and infectious sites: Potential for future theranostic system': [journal of controlled release 327 (2020) 737-746].

BACKGROUND: Therapeutic interventions for infectious and inflammatory diseases are becoming increasingly challenging in terms of therapeutic resistance and side-effects. Theranostic systems to ameliorate diagnosis and therapy are therefore highly warranted. The pathophysiological changes in inflammatory lesions provide an attractive basis for extravasation and accumulation of PEGylated liposomes. The objective of this study was to provide direct quantitative information on the theranostic potential of radiolabeled liposome for accumulation in inflammatory models using position emission tomography (PET). METHOD: Preclinical murine models of inflammation (turpentine and LPS), infection (Staphylococcus aureus) and collagen-induced arthritis (CIA) was established and monitored using bioluminescence imaging (BLI). Across all models PET imaging using radiolabeled PEGylated liposomes (64Cu-liposomes) were performed and evaluated in terms of accumulation properties in inflammatory and infectious lesions. RESULTS: BLI demonstrated that the inflammatory and infectious models were successfully established and provided information on lesion pathology. Activity of 64Cu-liposomes were increased in inflammatory and infectious lesions between early (10-min or 3-h) and late (24-h) PET scans, which validates that a continuous extravasation and accumulation of long circulation PEGylated liposomes occurs. CONCLUSION: The theranostic potential of long circulating PEGylated radiolabeled liposomes was shown in multiple preclinical models. Impressive accumulation was seen in both inflammatory and infectious lesions. These results are encouraging towards advancing PEGylated liposomes as imaging and drug delivery systems in inflammatory and infectious diseases.