Method and device to treat vulnerable plaque

Surgery – Instruments – Heat application

Reexamination Certificate

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C607S103000, C623S902000

Reexamination Certificate

active

06786904

ABSTRACT:

FIELD OF THE INVENTION
The present invention generally relates to cardiovascular medicine. More particularly, the present invention relates to a cardiovascular heat delivery device and a method to treat a vulnerable plaque tissue.
BACKGROUND OF THE INVENTION
Coronary artery disease (CAD) is the most important cause of morbidity and mortality in today's society. Atherosclerosis (the most common form of arteriosclerosis, marked by cholesterol-lipid-calcium deposits in arterial linings), “hardening” of the arteries caused by plaques and plaque lesions, is the cause of myocardial infarction (MI). Some plaques are “hard and solid”, and the others are “soft and squishy”. It's the soft variety that is to worry about. Recently, this soft plaque has been called “vulnerable plaque” because of its tendency to burst or rupture.
Ischemic heart disease represents a continuum from stable angina to unstable angina to non-Q-wave MI to Q-wave MI. Patients whose angina becomes unstable are classified as having acute coronary syndrome (ACS). It was formerly believed that thrombosis leading to critical occlusion of coronary arteries at the site of atherosclerotic plaque rupture was the common cause of ischemic heart disease. It is now thought, that even plaque lesions that do not critically occlude coronary arteries can cause MI. ACS can be caused by the rupture of an unstable atherosclerotic plaque. Vulnerable plaques are usually those causing only mild to moderate stenosis and having a lipid-rich core and a thin, macrophage-dense, collagen-poor fibrous cap. Factors affecting plaque rupture include mechanical injury, circadian rhythm, inflammation, and infection. Progressive thrombosis and vasospasm may follow plaque rupture.
In the past, it was believed that atherosclerosis gradually and progressively led to the complete occlusion of an artery, thereby causing acute coronary events. However, it is now believed that rupture of a nonstenotic, yet vulnerable atherosclerotic plaque, frequently leads to an acute coronary syndrome.
It has been reported that rupture-prone (i.e., vulnerable plaques) typically have
a thin fibrous cap,
numerous inflammatory cells,
a substantial lipid core, and
(surprisingly) few smooth muscle cells.
It is believed that physical disruption of such a plaque allows circulating blood coagulation factors to meet with the highly thrombogenic material in the plaque's lipid core, thereby instigating the formation of a potentially occluding and fatal thrombus. Some believe these plaques cause <50% cross-sectional stenosis of the artery.
While the concept of plaque “vulnerability” implies the ability towards thrombosis, the term “vulnerable” was originally intended to provide a morphologic description consistent with plaques that are likely to rupture and can be seen as a specific cause of acute coronary syndromes. The phrase ‘vulnerable plaque’ was coined in the early 90's by Dr. James Muller of the University of Kentucky when he was working in Boston. Muller picked the word from his work against the arms race. Missiles in silos were vulnerable to Russian attack because they can be destroyed before they are used. Muller described that rupture-prone plaques are vulnerable, because something can come along and cause them to “misfire”.
Mechanical stress and composition of plaques play an important role in plaque disruption. Mechanical forces can easily disrupt this plaque, even merely the vibration of the heart as it beats. The plaques are classified as either yellow or white using coronary angioscopy. Yellow plaques with an increased distensibility and a compensatory enlargement may be mechanically and structurally weak. As a result, mechanical “fatigue,” caused by repetitive stretching, may lead to plaque disruption. Plaques with a high distensibility and a compensatory enlargement may be vulnerable.
The development of vulnerable plaques is not limited to the localized lesions but is a pan-coronary process. In patients with MI, all three major coronary arteries are widely diseased and have multiple yellow though nondisrupted plaques.
While a rupturing plaque can lead to a heart attack, most of the time nothing much bad happens. In fact, it appears that plaques break or rupture all the time, and those that trigger heart attacks are unlucky exception. It is believed that the large plaques visible on angiograms are often the healed-over and more stable remains of small vulnerable plaques.
One of the most important issues of vulnerable plaque is the fact that vulnerable plaques do not bulge inward. Instead, as plaque grows, it often protrudes outward, into the wall of the artery, rather than into the channel-lumen where blood flows. On an angiogram, everything can look normal. But when dissected after death, the arteries' walls are thick with plaque that could not yet be seen by angiogram.
Imaging the coronary arteries is a challenging task. The coronary arteries are difficult targets to track because of their small size, their tortuous course along the myocardium, and their complex cyclic excursions with cardiac and respiratory motions over distances much larger than their lumen size. Most limiting of all, motion, if not compensated, generates blurring and ghosting interferences not only from the coronary vessels themselves but also from the surrounding tissues. The key to succeed in imaging these highly mobile vessels is, thus, to freeze the motion. The development of ultrafast MRI has enabled steady progress to be made in coronary imaging by several groups in recent years. Among the various proposed methods the most successful are the segmented turbo-FLASH and spiral-scan gradient-echo techniques. Each produces a 2D image of the coronary arteries within a single breath-hold, acquiring 16-20 segments or spirals through k space in consecutive heart-beats. In order to freeze vessel motion each combines cardiac gating and breath holding and acquires the information exclusively during mid-diastole, the most quiescent period in the cardiac cycle.
By collecting a 2D image in less then 60 ms, EPI (Echo Planar Imaging) combined with a time-of-flight (TOF) EPI method offers a unique way to completely freeze the effect of both cardiac and respiratory motions.
At present, methods are being developed which allow a physician to view vulnerable plaque. Several invasive and non-invasive imaging techniques are available to assess atherosclerotic disease vessels. Most of these techniques are strong in identifying the morphological features of the disease, such as lumenal diameter and stenosis or wall thickness, and in some cases provide an assessment of the relative risk associated with the atherosclerotic disease. However, none of these techniques can yet fully characterize the composition of the atherosclerotic plaque in the vessel wall and, therefore, are incapable of conclusively identifying the vulnerable plaques.
High-resolution, multi-contrast, magnetic resonance (MR) can non-invasively image vulnerable plaques and characterize plaques in terms of lipid and fibrous content and identify the presence of thrombus or calcium. Application of MR imaging opens up whole new areas for diagnosis, prevention, and treatment of atherosclerosis.
Magnetic resonance imaging is proving to be a very useful non-invasive imaging technique in the study of the long-term evolution of atheroma lesions. Not only is it applicable for the diagnosis of atherosclerotic disease but also for the characterization of the cellular mechanisms implied in the development of vascular damage. The four main stages of lesions found in atherosclerosis, i.e. the onset of the lesion with the appearance of remodeling, the development of vulnerable plaque, thrombus formation, and the organization of the thrombus by connective tissue, have been reported, in both experimental animal models and in humans, from the images obtained by Magnetic Resonance Imaging (MRI). High-resolution, multi contrast MRI can non-invasively image vulnerable plaques and characterize plaques in terms of their different components (i.e.

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