Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.6 (CAD)
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When regional myocardial dysfunction is present, the physiological pattern of ventricular filling and contraction is impaired. During acute coronary occlusion, characteristic changes are observed in the ischemic myocardial segment: the amplitude of the systolic wall thickening is reduced (hypokinesia), then virtually absent (akinesia) and finally replaced by a paradoxical outward motion (dyskinesia). The maximum amplitude is reached in early diastole ("post-ejection thickening"). Since hyperkinesis develops in the normal region, the ischemic and the normal region contract asynchronously. Experimentally left ventricular asynchrony can be detected by means of subendo- and subepicardially implanted ultrasonic crystals ("sonomicrometry") or by the analysis of the phase difference of the first Fourier harmonic of dysfunctional versus control myocardial wall motion. In the clinical setting, digitized cineventriculography, radionuclide angiography and digitized M-mode echocardiography were used to assess left ventricular asynchrony in patients with coronary artery disease and hypertrophic cardiomyopathy. However, these imaging modalities are time-consuming and require complicated off-line analysis. Tissue Doppler echocardiography (TDE) is a new ultrasound modality that is based on color Doppler principles and allows for quantification of myocardial wall motion velocity by detection of consecutive phase shifts of the ultrasound signal reflected from the myocardium. The Doppler signals are displayed as a color or pulsed Doppler image by rejecting low-amplitude echoes from the blood pool due to changes in thresholding and filtering algorithms. In addition, the ability to measure low velocity is improved in the TDE system so that the lowest measurable velocity is 0.2 cm/s, a velocity level associated with cardiac tissue motion (Table 1). Due to its high temporal and spatial resolution, TDE provides valuable information on regional myocardial wall motion during different intervals of the cardiac cycle. In healthy subjects, patients with coronary artery disease and patients with hypertrophic cardiomyopathy, tissue Doppler echocardiography was used to assess myocardial synchrony/asynchrony on a 2-fold temporal and spatial analysis. Peak myocardial velocities in different myocardial regions were detected during rapid ejection, isovolumic relaxation, rapid filling and atrial contraction (Figure 1). In the apical view, during the isovolumic relaxation time (IVRT) healthy subjects showed slow, synchronous outward motion of the septum and the lateral wall with homogeneous color-encoding (blue/green, Figure 2). Analysis of peak velocities revealed low, negative velocities in both the septum and the lateral wall (Figure 3). In patients with a significant luminal narrowing of the LAD myocardial asynchrony was detected during the isovolumic relaxation period: while the septum was moving inwards (red color-encoding with low, positive velocities), the lateral wall was moving outwards (blue/green encoding, low, negative velocities). A representative example of a patient with CAD is given in Figure 4. The M-mode analysis of the abnormally contracting interventricular septum reveals positive peak tissue velocities during the isovolumic relaxation period (Figure 5). In hypertrophic cardiomyopathy, TDE was able to detect an abnormal inward motion of the interventricular septum during IVRT and a delay in the onset of rapid filling (Figure 6). Thus, tissue Doppler echocardiography is a feasible method for the on-line detection of myocardial asynchrony. Sensitivity and specificity of the findings have to be explored in further, prospectively randomized trials.
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PMID:[Asynchrony of ventricular contraction and relaxation--pathophysiologically recognized phenomenon, now can be clinically assessed]. 1002 85

In this article we have outlined the current rationale and role of invasive management in ACS. For the majority of patients with ACS, who are either at high risk or unstable, invasive management is a critical element in breaking the sequence of recurrent ischemia leading to early cardiac events (Fig. 11). Secular trends in the care of cardiovascular patients predict even more sophisticated, invasive methods of treating coronary occlusion in the future. A futurist's view on this subject may envision the following type of scenario. A patient with prior CAD experiences persistent chest pain and notifies the emergency medical system. The paramedics arrive, and perform a rapid fingerstick cardiac biomarker panel and ECG. The results are interpreted by an emergency physician via a telecommunication system, and the patient is determined to be at high risk. He or she is triaged to a center capable of angioplasty and bypass surgery. On the way to the hospital, the patient is treated with aspirin, IV heparin, and an IV glycoprotein IIb/IIIa inhibitor. The patient undergoes triage angiography within 1 hour of hospital arrival, culprit lesion(s) are identified, and a revascularization plan is made--setting a critical pathway that is definitive. This vision is not far off on the horizon. We anticipate additional clinical trial results will help form the decision points in this optimal treatment scenario, which for a large proportion of patients will involve invasive management.
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PMID:Early use of coronary angiography and intervention. 1038 33

There are no perfect tests or algorithms to exclude ACI. Because acute coronary occlusion often occurs in patients with low-grade coronary stenosis, the diagnostic goal of a chest pain diagnostic protocol is not to identify patients with CAD, but rather to identify patients who may be safely discharged home without the development of complications such as MI, unstable angina, death, shock, or CHF over the next 1 to 6 months. There is an advantage to evaluating patients at the time of their symptoms. Patients who have a small plaque that is ruptured, leading to intracoronary thrombosis and ischemia, will manifest ischemia on diagnostic testing that could missed in routine outpatient testing when their plaque were stable. The diagnosis and risk stratification of acute coronary ischemia in the ED depends on a careful history and interpretation of the ECG. Multiple regression models using readily available data (e.g., history, physical examination, and ECG) provide the best tools for risk stratification. If one is deciding how to select patients for an EDOU chest pain evaluation, diagnostic tools that have previously been tested and validated in this setting are preferable. These include the Multicenter Chest Pain Study derived tools (i.e., Goldman, Lee), the ACI and ACI-TIPI tools, and sestamibi risk stratification tools. This is not to say that other tools may not play a role at individual institutions. It is probably better to select a consistent approach and evaluate its performance, rather than to allow random variation to dictate practice. The future direction probably will involve standardization of the ED chest pain population. This allows outcome and cost-effectiveness comparative research of various strategies for patients with normal or nondiagnostic ECGs and normal biomarkers. Although this approach allows more precise stratification, the risk will never be zero, meaning that there will never be a substitute for good clinical judgment and close follow-up care.
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PMID:Identification of chest pain patients appropriate for an emergency department observation unit. 1121 3

The selective hand injection of contrast media into the right coronary artery of a middle-aged male by Doctor F. Mason Sones on October 30, 1958 introduced a new era in Cardiovascular Medicine. It is the purpose of this presentation to portray the pivotal role the coronary angiogram has played in creating some of the epochal events and discoveries that have characterized the march of progress in the field of cardiology over the past five decades. As the first reliable in vivo marker for the presence of obstructing coronary lesions, the coronary angiogram importantly led to our first studies of the natural history of patients with CAD. The motion studies afforded by cineangiography also permitted dynamic visualization of the contracting ventricle which led to the concept of regional wall motion abnormalities being characteristic of CAD and provided some of our earliest understanding of left ventricular dysfunction. The coronary angiogram also provided the stimulus for the development of aorto-coronary bypass surgery that was introduced by Dr. Rene Favaloro in May 1967. Subsequently, Dr. Andreas Gruntzig astounded the cardiology world by reporting his new percutaneous method of achieving revascularization (PTCA). The coronary angiogram provided the road map necessary for the successful deployment and application of this balloon technology that was soon to rival CABG surgery. The thrombolytic era was heralded in July 1979 when Dr. Peter Rentrop documented the successful reperfusion of a coronary artery in a 57-year old man by first recanalizing the occluding thrombus with a guidewire and then infusing the proteolytic enzyme, streptokinase directly into the artery. Within a year, DeWood made the angiographic observation that spontaneous regression of the totally occluding thrombus occurred among patients undergoing coronary arteriography within the first 24 hours of the onset of symptoms of an acute myocardial infarction. This led to the earliest studies on clot lysis by fibrinolytic agents and also paved the way for the balloon catheter to be used as a mechanical means of achieving coronary reperfusion in the acute setting. In the 1980s it was realized that vigorous lipid lowering with statin drugs did little to effect regression of the established atherosclerotic lesion but it did result in a dramatic decrease in subsequent clinical cardiovascular events. Similar observations were made by Little and others that acute coronary occlusion resulted more often from young, non-obstructing atheromatous lesions than it did from high grade obstructive lesions. This incriminated rupture of the soft, lipid rich atheromatous plaque as the most common mechanism leading to acute MI. In the closing decade of the past century, estimates of coronary blood flow using TIMI flow grades and TIMI frame rates led to the central unifying concept that the early restoration of normal flow (TIMI grade 3) was linearly related to survival after reperfusion therapy whether it be achieved pharmacologically or mechanically. The coronary angiogram was also integral in establishing antiplatelet therapy as the preferred pharmacotherapeutic agents to be used in association with stent deployment compared to coumarin drugs in preventing stent thrombosis. Although the coronary catheter is now used to deliver newer intracoronary devices such as intravascular ultrasound, velocity probes, gene probes and eluting catheters, it has served as the one indispensable form of coronary imaging for five successive decades. As such it has provided far more than is implied by the term "lumenology" and can rightly be called the lumen de lumine, the light of lights, for cardiovascular medicine.
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PMID:The coronary angiogram and its seminal contributions to cardiovascular medicine over five decades. 1205 14

The increased operative mortality and morbidity of women compared with men undergoing CABG surgery results from multiple differences in presentation, preoperative risk profile, and surgical factors. Investigators have found consistently that women present with a different preoperative risk profile than do men. Women more commonly have factors associated with increased short- and long-term mortality, such as less frequent use of IMA grafts. Differences in study design and patient population may contribute to variability in short- and long-term mortality among the various studies. The lack of representation of women in older clinical trials has hindered our understanding of the management of CAD in women; this situation must be remedied in future studies, [95]. Known physiologic and anatomic differences must be evaluated for their effects on outcomes. Further studies are needed to evaluate gender-related differences in autonomic responses to acute coronary occlusion, complications related to cardiopulmonary bypass, susceptibility to abnormalities in coagulation, and other factors that might account for discrepant outcomes in men versus women undergoing CABG [96]. Beyond these factors, specific pharmacologic and therapeutic considerations, such as the role of estrogen replacement therapy, need to be clarified. As further knowledge accumulates, it is hoped that gender-specific risk factors can be mitigated and protective factors exploited, thereby improving the outcomes for all cardiac surgery patients.
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PMID:Gender and cardiac surgery. 1456 72

This review focuses on optimal use of PET and PET-CT in monitoring medical and interventional therapy in patients with CAD. PET provides quantitative measurement of absolute myocardial blood flow and thus permits comprehensive physiological assessment of the coronary circulation. Hybrid PET-CT, in particular CCTA, adds anatomical information to maximal MBF measurement and so facilitates distinction of triple vessel focal epicardial disease from coronary microvascular disease or diffuse coronary atherosclerosis without focal stenoses. Hybrid PET-CT also may be of value in determining appropriateness and feasibility of percutaneous interventional therapy for chronic total coronary occlusion. PET alone, however, is the preferred modality to address functional status of the coronary circulation and response over time, if required, to medical or interventional therapy. CT at a minimum provides attenuation correction. More detailed CCTA should be added only when a well-defined need for anatomical information is required to answer the clinical question posed.
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PMID:Cardiac PET-CT for monitoring medical and interventional therapy in patients with CAD: PET alone versus hybrid PET-CT? 2446 5