Acute Coronary Syndrome

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Original Editors - Students from Glasgow Caledonian University's Cardiorespiratory Therapeutics Project.

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Definition/Description

"Acute coronary syndromes (ACSs) comprise a spectrum of conditions that typically arise from atherothrombosis, includingunstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). The health care burden associated with ACS is well-known, with an estimated 785 000 new events, 470 000 recurrent events, and 195 000 silent events predicted for the current year alone.1 Either spontaneous or percutaneous coronary intervention (PCI)-induced atherosclerotic plaque rupture can incite the atherothrombotic process. The ensuing platelet response to vascular injury is pivotal and is characterized by adhesion of circulating platelets to the vascular endothelium, subsequent activation and aggregation of platelets, and potential obstruction
of the intravascular lumen." (ART 2)

Epidemiology

"Acute coronary syndromes (ACS) are the leading cause of death in older adults, aged 65 years or older". (ART 1)

"In the 7MM, the hospitalized incident cases of ACS will increase from 1.29 million cases in 2012 to 1.43 million cases in 2022 at the rate of 1.04% per year. The US constitutes around 40% of the total hospitalized incident ACS cases in the 7MM and will be the market with the highest number of cases during the forecast period. The majority of the cases occurred in men (58.15%) and in those ages = 65 years (69.01%). For the 7MM, about 33% of the ACS cases were STEMI, 44% were NSTEMI, and 23% were UA. The proportions varied depending on the market."(ART 6)

"Older adults with ACS who present without chest pain are more likely to die in the hospital compared with patients aged younger than 65 years with chest pain.3,4,9-11 In fact, older women with chest pain or discomfort are twice as likely to die in the hospital compared with younger women with the same complaint (13% vs 3.7%, P < .001).4 Similarly, older men with chest pain are twice as likely to die in the hospital as men aged younger than 65 years with chest pain (6.6% vs 2.4%, P < .001).4

Older women with ACS who present without chest pain have a 6-fold increase in hospital mortality rate compared to women less than age 65 years with chest pain (21.2% vs 3.7%, P < .001).4 Furthermore, older men without chest pain are more likely to die in the hospital compared with men aged younger than 65 years with chest pain (22% vs 2.4%, P < .001).4 High mortality rates may be due to delays in PCI with fewer lifesaving treatments. Primary PCI for older adults with ACS is between 6% and 60%.3,4,9-11 The time to primary PCI of up to 162 minutes4,9 exceeds the recommended 90 minutes.22" (art 1)

Background epidemiology to the disease or condition (to include prevalence and incidence as appropriate from a UK or Scottish perspective. (You may want to also look at the disease prevalence across different social economic groups).

Aetiology

Vascular injury and thrombus formation are key components in the initiation and progression of atherosclerosis and in pathogenesis of acute coronary syndrome (Epstein, 1992). Atherosclerotic plaque formation occurs as a result of damage to the endothelium of the blood vessel. The damaged endothelium stimulates a cascade of inflammatory events that causes macrophages to digest low-density lipoprotein (LDL) transforming into foam cells and causing formation of fatty streaks in the subendothelium (Kumar, 2009). Several coronary risk factors can influence this process, including hypercholesterolemia, hypertension, diabetes, and smoking (Kumar, 2009). ACS takes place when a disrupted atherosclerotic plaque in a coronary artery stimulates platelet aggregation and thrombus formation. Previous research has suggested that the narrowing of the coronary artery causes a decrease in blood flow and ultimately ischemia, however, recent studies have suggested that the rupture of an unstable atherosclerotic plaque is chiefly responsible for thrombus formation and infarction. Autopsy studies have shown that plaque rupture causes approximately 75% of fatal myocardial infarction in comparison to superficial endothelial erosions which account for only 25% (Davies, 1990).

Investigations

Imaging Techniques

Echocardiography
"Echocardiography can rapidly assess for RWMA, is highly portable, and relatively inexpensive compared with other noninvasive modalities. Echocardiography relies on detecting wall motion changes, which occur when myocardial blood flow falls below resting levels. Often this occurs when coronary obstruction exceeds 85–90% of the luminal area [5]. Myocardial blood flow affects myocardial oxygen consumption. When there is a supply-demand mismatch, myocardial contractility is affected and leads to the development of hypokinesis [6]. Echocardiography is a class I indication to evaluate RWMA in patients presenting with chest pain but with low-to-intermediate risk. Earlier discussions have revealed that echocardiography had a high sensitivity (92-93%) in detecting AMI and cardiac ischemia (88%) in patients presenting to the ED with chest pain [7]. The specificity was only 53–57% in this same group. The addition of contrast echocardiography has been employed to improve these parameters. Myocardial contrast echocardiography (MCE) has been used to evaluate RWMA and to assess microvascular perfusion. A decrease in myocardial blood flow (MBF) results in a reduction in myocardial blood volume, and with MCE a perfusion defect can be visualized. Evaluation of MCE in a multicenter study when compared with single photon emitted computed tomography found that the two were similar in their ability to identify and diagnose those with AMI [8]. Lønnebakken et al. [9] used MCE to prioritize patients with NSTEMI and angiographically severe CAD. Their study used a wall motion score compromising the 17 segments left ventricular model and myocardial perfusion followed by CAD assessment invasively measured by quantitative coronary analysis (QCA). Results from this study found that patients with ≥6 hypoperfused left ventricular segments had a 7-fold higher risk of severe CAD. Their findings were not specific for the area of stenosis unless it involved the proximal left anterior descending (LAD) coronary artery. Limitations in echocardiography are often the result of limited or poor acoustic windows, its poor specificity, operator-dependent acquisition, and is one of the most subjective imaging modalities."(art3)

Computed Tomography
"MDCT has been studied extensively to determine its role in the noninvasive assessment of ACS. MDCT has the ability to identify plaque area and the degree of stenosis. The sensitivity of MDCT to detect CAD has been reported to be 73–100% with a specificity of 91–97% [10–12]. MDCT has good correlation with IVUS [13] and coronary angiography [14]. A study by Hoffmann et al. [15] used MDCT to compare lesion characteristics in culprit lesions from patients with ACS, stable lesions in patients with ACS, and stable lesions in patients with stable angina. Lesions that were detected by MDCT correlated well to coronary angiography thus possibly serving as a method to further risk stratify patients with ACS. All lesions that had impaired image quality were not included in the analysis. MDCT studies have also sought to define the high-risk characteristics in lesions that may make patients more susceptible to ACS. Detection of low attenuation of <30 Hounsfield units and positive remodeling has proven very accurate in predicting future ACS [16]. Recent work [17] has shown that MDCT can predict thin cap fibroatheromas (TCFA) and vulnerable plaque by identifying low attenuation, a large remodeling index, and a signet ring-like appearance. These predictors correlated well with OCT. Motoyama et al. [16] studied coronary artery lesions in patients with NSTEMI, STEMI, or unstable angina presenting >24 hours after symptoms onset whom were symptom-free and hemodynamically stable. Culprit lesions in patients with ACS are characterized by large plaque volume, necrotic cores and local inflammation. MDCT studies with IVUS and OCT have also confirmed that high attenuation around the coronary artery plaque was more susceptible to rupture [18]. MDCT is limited by its inability to image lesions with heavy calcium burden, necessitates the use of intravenous contrast, and requires radiation exposure. The greatest asset of MDCT may be the negative predictive value for excluding significant CAD in those at low-to-intermediate risk presenting with chest pain." (art3)

Cardiac Magnetic Resonance Imaging
"The role of CMR has clear roles in the congenital heart disease, chronic CAD, myocardial and pericardial diseases, and imaging of the great vessels. CMR has a sensitivity of 84% and a specificity of 85%, which is greater than EKG or troponin and more specific than an abnormal troponin [19]. There are multiple methods that CMR employs to establish a diagnosis of ACS. CMR cine imaging can assess global and regional left ventricular function, and its accurate and reproducible ventricular volumes and functions make it more accurate than other noninvasive methods [20]. First pass myocardial perfusion utilizes a contrast agent coadministered with a vasodilator-like adenosine to delineate under perfused areas highlighting subendocardial ischemia. The MR-IMPACT study evaluated 234 patients with CMR and SPECT, and CMR was better at detecting coronary artery stenosis than SPECT [21]. CMR has been used to evaluate microvascular obstruction (MVO). Imaging within the first few minutes of contrast administration can detect MVO by revealing decreased contrast delivery to the infarcted area and decreased signal intensity on T1-weighted imaging. Myocardium that is acutely or chronically infarcted that does not have MVO will retain contrast and have bright signal intensity on T1-weighted images. Viability can be assessed utilizing CMR via late gadolinium enhancement. Ten to twenty minutes after contrast administration, delayed imaging can highlight the extent of the scar and potential for functional recovery. CMR can also detect myocardial edema often present in acute injury with T2-weighted images, and coronary CMR angiography can detect proximal coronary artery stenosis. The evaluation of CMR as an imaging modality for the stratification of patients presenting to the ED with chest pain has been extensively evaluated, and it can identify ACS more predictably than EKG, troponin, and TIMI score [19]. Plein et al. [22] studied NSTEMI patients 2–5 days after presentation and concluded that CMR reliably predicted coronary stenosis necessitating revascularization confirmed by angiography. CMR also can fill a vital role in differentiating ACS from other myocardial diseases such as myocarditis and can detect complications from ACS such as left ventricular thrombus, ventricular septal defects, and aneurysms [23]. Despite advances in CMR techniques several limitations persist. Acquisition times are lengthy, unstable patients and patients without new generation pacemakers or with metallic fragments are not candidates, and it is relatively expensive, and is not portable. CMR with its limitations still remains a viable option in the diagnosis and stratification of patients presenting with chest pain." (art3)

Positron Emission Tomography
"PET with 18F-fluorodeoxyglucose (FDG) is able to identify functional metabolic activity by imaging glucose utilization. FDG once injected is taken up by cells that utilize glucose for metabolism, and the more metabolic activity of the tissue the greater the amount of FDG, taken up. As FDG decays gamma rays are emitted and the position of origin is imaged by PET imaging. The majority of FDG PET for cardiac applications is assessing viability, but interest in its use for ACS has arisen due to its high sensitivity for molecular targets. Imaging with PET in ACS relies on the ability to detect acute inflammation. Atherosclerotic coronary plaques are characterized by macrophage accumulation. FDG uptake is increased in these areas as macrophages often take up more glucose than the surrounding tissues [24, 25]. PET has limited spatial resolution of 3–5 mm making reproducible measurements in the right coronary artery (RCA) and mid to distal vessels somewhat problematic. PET is further limited as it uses ionizing radiation, requires coregistration with CT or MRI for localization, and is hindered by cardiac and respiratory motion [26, 27]. Studies employing a diet rich in free fatty acids prior to imaging leads to a decrease in myocardial uptake of tracer without affecting other tissue improving coronary artery imaging [28]. PET, due to its ability to detect increased metabolic activity, may help identify vulnerable high risk plaque that is not obstructive to blood flow due to positive remodeling, but still prone to rupture and subsequent ACS." art3

Single Photon Emission Computed Tomography
"Myocardial perfusion imaging has long been used for the detection of ischemia and even viability. Resting and stress myocardial perfusion imaging in patients with low-to-intermediate risk for CAD will identify active inducible ischemia; however, in patients with recent angina symptoms SPECT may not be able to identify recent and old infarcts limiting its specificity. SPECT is more sensitive than exercise treadmill testing alone for detecting coronary artery stenosis of >50% with a sensitivity of 87% and a specificity of 73%, and with vasodilator stress the sensitivity is 89% and specificity is 75% [29]. There is much less operator dependency with SPECT imaging, and simultaneous assessment of regional perfusion and function can be obtained. A study performed in patients with chest pain randomization to resting SPECT did not alter or affect treatment decisions in patients with an eventual diagnosis of AMI or UA. SPECT did reduce the rate of admissions in those without ACS [30]. Limitations with SPECT are that it has imaging protocols up to 4 hours for stress rest comparison, necessitates radiation exposure, has a lower spatial resolution than echocardiography, can underestimate three vessel coronary artery disease due to balanced ischemia, and can produce many attenuation artifacts."art 3

Invasive Imaging Techniques: IVUS and OCT
"Several invasive methods exist to detect and characterize vulnerable plaque in patients with CHD and IVUS, and OCT will be discussed further here. Our understanding of plaque progression and vulnerable plaque characteristics has been greatly enhanced with IVUS/IVUS virtual histology (VH) and OCT. In the PROSPECT study, patients presenting with ACS underwent coronary angiography and IVUS after PCI. During the 3 year followup, there was a 20% risk of major adverse cardiovascular events (MACEs) including 13% in culprit lesions and 12% in nonculprit lesions [31]. The greatest predictors of this risk were a large plaque burden of ≥70%, minimal luminal area (MLA) ≤4 mm by IVUS with large necrotic core or TCFA. The highest risk was in patients with TCFA, increased plaque burden, and decreased MLA. Patients with long plaques ∼12 mm had increased risk as well. IVUS allows in vivo wall visualization and the differentiation of morphological characteristics between culprit and nonculprit plaques [32]. In a study with serial IVUS imaging over 12 months ∼75% of TCFA heal during followup or evolve to less vulnerable plaques. TCFA may develop from pathological intimal thickening and thick cap fibroatheromas (ThCFA), and disease progression is more likely with increased plaque volume [33]. Limits in IVUS utilization are that it is invasive and thus not ideal for those not undergoing angiography. IVUS has the inability to detect TCFA (<65 μm) due to its limited spatial resolution of >100 μm, and an inability to accurately distinguish plaque components [34]. OCT, on the other hand, has high resolution of 10 to 20 μm, ∼10 times that of IVUS [35]. In ACS, OCT has identified culprit lesions in STEMI patients when compared to NSTEMI patients who have more plaque rupture, TCFA, and red thrombus. Unstable plaques are defined by TCFA. A cap of <65 μm has been observed in 95% of ruptured plaques [36]. OCT is able to identify rupture-prone plaques by clearly visualizing large lipid cores, TCFA, and assess inflammation [37]. OCT is limited as it is invasive, has limited depth penetration making it poor at delineating lipid content, and is time consuming in that each coronary artery must be imaged separately. Although IVUS and OCT require an invasive approach to detect high-risk plaque characteristics they have been vital in our understanding of these high-risk indicators and have enabled further characteristics to be defined by noninvasive measures." art 3

Clinical Manifestations

The extent to which a coronary artery is occluded often correlates with presenting symptoms and diagnostic findings. Angina or chest pain is considered the cardinal symptom of ACS. Other symptoms that are commonly associated with ACS include; pain with or without radiation to left arm, neck, back or epigastric area, shortness of breath (SOB), diaphoresis, nausea and light headedness. It is important to note that women often present with atypical symptoms which may ultimately delay diagnosis and treatment. These clinical manifestations include; fatigue, lethargy, indigestion, anxiety and pain radiating down the back.

Physiotherapy and Other Management

Anti-Platelet therapy is common management provided by other healthcare professionals. This generally involves the utilzation of medications, predominately in tablet form. These drugs can be aspirin, adenosine diphosphate (ADP)-receptor blockers and aglycoprotein IIb/IIIa inhibitors, among others(ART 2).

Asprin

"Aspirin (acetylsalicylic acid [ASA]) blocks the synthesis of TxA2 from arachadonic acid via its inhibition of the cyclooxygenase (COX) enzyme. It represents the oldest and most studied antiplatelet agent, with early clinical trials in ACS showing consistent benefit over placebo or untreated control for reducing the risk of death and recurrent MI." (ART 2)

Adenosine Diphosphate-Receptor Antagonists

"The joint interaction of ADP with its P2Y1 and P2Y12 receptors not only induces platelet aggregation but also amplifies the platelet response through enhanced secretion of, and response to, platelet agonists such as TxA2 and thrombin.15 Consequently, clopidogrel and other thienopyridines, which specifically and irreversibly inhibit the ADP P2Y12 receptor subtype, have become increasingly important in the management of ACS. Several newer antiplatelet agents also act via P2Y12 antagonism and show promise for assuming greater roles in ACS therapy." (ART2)

Ticlopidine

"Ticlopidine was developed as the original ADP P2Y12 receptor antagonist.16 Clinical trials have shown its superiority over control, and its equivalence to aspirin in the prevention of secondary vascular events in patients with ACS.17,18 The concept of combining ASA and a thienopyridine for ACS management was first assessed using ticlopidine, with several studies in patients with PCI demonstrating the benefit of dual antiplatelet therapy over ASA alone or ASA plus warfarin.19-23 However, ticlopidine is associated with elevated risks of neutropenia and thrombotic thrombocyptopenic purpura (TTP) and is poorly tolerated with associated increases in nausea and vomiting." (ART 2)

Clopidogrel

"Establishing the benefit of clopidogrel in UA/NSTEMI. The Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial was the first large randomized clinical trial to establish the benefit of clopidogrel in secondary prevention. The trial compared clopidogrel (75 mg/d) against ASA (325 mg/d) in 19 185 patients with recent MI, recent ischemic stroke, or established peripheral arterial disease (PAD). There was an observed 8.7% relative risk reduction in patients receiving clopidogrel versus ASA for the composite end point of vascular death, MI, or stroke (5.32% vs 5.83%, P ¼ .04).27 Subgroups of the CAPRIE trial with diabetes mellitus, prior coronary artery bypass graft (CABG) surgery, or prior history of MI or ischemic stroke showed particular benefit with clopidogrel as opposed to aspirin therapy." (ART 2)

Prevention

Brief consideration of how this pathology could be prevented and the physiotherapy role in health promotion in relation to prevention of disease or disease progression.

Resources

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Recent Related Research (from Pubmed)

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References

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