Evaluation of presence of and vulnerability to atrial fibrillation and other indications using matrix metalloproteinase-based imaging

Abstract

The invention provides, in some embodiments, methods relating to assessing increased risk of developing atrial fibrillation (AF), and/or the likelihood of responding to particular AF therapies using imaging agents comprising an MMP inhibitor linked to an imaging moiety. The invention further provides methods for evaluating the presence of the risk of developing other cardiovascular conditions and assessing the effectiveness of treatment or other intervention for such conditions by determining MMP levels.

Description

BACKGROUND OF INVENTION[0001]Atrial fibrillation (AF) is a disturbance in the rhythmic beating (or arrhythmia) of the upper chambers of the heart. AF is the most common sustained cardiac arrhythmia, responsible for almost 50% of hospitalizations for arrhythmias (Benjamin E J, et al. 1998; Wyse D G, et al. 2002; Benjamin E J, et al. 1997; Allessie M A, et al. 2001). Consequently, AF is a significant cause of morbidity and mortality and treatment of AF has been hampered by the ineffectiveness of available drugs. Moreover, attempts to terminate AF with electrical shocks, using a process termed “cardioversion” works for only about one-half of the patients during the first 6-12 months. Therefore, a “simple” means to identify patients in whom cardioversion would effectively terminate AF would be beneficial in terms of saved time and money. Moreover, a means to identify patients that may or may not benefit from an implantable pacer, pharmacological rate and / or rhythm control therapy and / or...

AI Technical Summary

Benefits of technology

[0026]In another aspect, the invention provides methods of determining the presence of calcific aortic valve disease (CAVD) in a subject and / or determining a subject's risk of developing CAVD comprising administering to a subject an imaging agent comprising an MMP inhibitor linked to an imaging moiety and acquiring a first cardiac image of the subject; and determining the presence of CAVD and / or a subject's risk of developing CAVD based at least in part on the first cardiac image. The cardiac image typically includes or is of the cardiac valve, optionally including the leaflets. In accordance with the invention, increased uptake of the imaging agent in the aortic valve region is indicative of the presence of CAVD or the increased risk of developing CAVD. In some embodiments, the subject being imaged does not have atherosclerosis (e.g., the subject does not manifest symptoms associated with atherosclerosis, and is referred to as “asymptomatic” for this condition). The uptake of an MMP inhibitor linked to an imaging moiety in a particular portion of a subject can allow for the imaging of tissue remodeling characterized in part by macrophage infiltration, MMP activation, and the like, in a portion of the subject, as a diagnostic indicator of CAVD.

Problems solved by technology

It has not been heretofore known that MMP levels could be detected at such early time points and that detection at these early time points correlated with increased risk of, for example, AF and CAVD.

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