CONFLICT OF INTEREST

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Lithuanian University of Health Sciences Faculty of Medicine Department of Radiology

Title of Master’s Thesis:

Cardiac computer tomography in Emergency settings

A Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree Master of Medicine Lithuanian University of Health Sciences

Author: Mohammad Asif Malik Supervisor: Dr. Antanas Jankauskas

Kaunas 2017-2018

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SUMMARY

Author name: Mohammad Asif Malik

Research title: Cardiac Computed Tomography in Emergency settings

Aim: To analyze and review the use of cardiac CT during acute chest pain in ED settings Objectives: To evaluate diagnostic value, advantages and disadvantages of calcium score in emergency settings, coronary CT angiography and triple rule out study in emergency settings

Methodology: This was a Systematic Literature review where searches were conducted using several databases: Medline (PubMed), science direct publications and UpToDate. All articles published from 2008 were included in the searches with no more than 10 years search criteria used. The search terms used were: ‘cardiac CT,' ‘cardiac CT in the emergency setting,' ‘CT angiography in the emergency settings,' ‘calcium score in emergency settings,' ‘Triple rule out in emergency settings.' Keywords were matched to database indexing terms. In PubMed, the related articles were also retrieved and added to this review.

Results: 3 out 5 studies about coronary artery calcium scoring showed a negative predictive value of (99%) in patient with low – intermediate risk with CAC score of 0.

The other studies found a substantial occurrence of CAD in patients with no CAC (7%) and with a low CAC score (17%). A study included high-risk patients; with 5 out of 13 (39%) patients who had a CAC score of 0 also had severe CAD.

All 4 studies (1 of them was metaanalysis) about CCTA showed a significant reduction in diagnostic evaluation time, reduction in the risk of ACS and rates of a repeated visit with 95 % CI. These studies have shown the safety and efficiency of CCTA for the triage of patient presenting to the emergency department with thorax pain and a low to middle risk of ACS. These studies have shown CCTA to have a high sensitivity (86– 100%) and a high negative predictive value (93– 100%).

4 studies assessed the image quality of TRO CT compared to dedicated to CT Image quality was not significantly different between the two groups (OR = 0.78, 95% CI = 0.58 to 1.06; I² = 0%)and in the rates of repeated ED visit. No significant difference was observed in image quality between TRO and

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4 Conclusions: Coronary artery calcium score has shown to have excellent negative predictive value in asymptomatic patients, but in case of acute chest pain there are no confident recommendations because ACS can be determined by non-calcified plaque; coronary CT angiography significantly shortens time to diagnosis, high sensitivity, high negative predictive value and reduces costs. CCTA has shown to be safe and effective for a patient presenting to emergency department with thorax pain and low to

intermediate risk of ACS; TRO study is more universal, but it is also more difficult to perform technically, so it should be reserved for patients with the unspecific clinical pattern.

Keywords: Cardiac CT; TRO CT in emergency settings; Acute chest Pain; Coronary Artery Calcium Scoring in emergency settings; coronary CT angiography in emergency settings;

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SANTRAUKA

Autorius: Mohammad Asif Malik

Darbo pavadinimas: Skubaus širdies KT tyrimo vertė

Darbo tikslas: Išanalizuoti ir apžvelgti skubaus širdies KT tyrimo vertę esant ūmiam krūtinės skausmui

Uždaviniai: Įvertinti kalcio indekso tyrimo, vainikinių arterijų KT angiografijos ir trigubo atmetimo tyrimo diagnostinę vertę, privalumus ir trūkumus esant ūmiam krūtinės ląstos skausmui

Metodika: Buvo atlikta sisteminė literatūros apžvalga, paieškos keliose duomenų bazėse: Medline (PubMed), Science Direct ir UpToDate. Į paiešką įtraukti straipsniai, publikuoti nuo 2008 m., įtraukiant ne senesnius nei 10 metų senumo straipsnius. Paieškos raktažodžiai buvo: ‘cardiac CT,'

‘cardiac CT in the emergency setting,' ‘CT angiography in the emergency settings,' ‘calcium score in emergency settings,' ‘Triple rule out in emergency settings.' Atitinkami straipsniai taip pat buvo pridėti ir iš PubMed duomenų bazės.

Rezultatai: 3 ir 5 studijų, analizuojančių kalcio indekso prognostinę vertę, gauta labai aukšta neigiamo kalcio kiekio prognostinė vertė (99 poc.), žemos ir vidutinės rizikos pacientų grupėje, esant kalcio indeksui 0. Tuo tarpu kitos studijos pateikė žemesnę prognostinę vertę – vienoje jų išeminė širdies liga nustatyta 7 proc. pacientų be kalcifikacijos požymių vainikinėse arterijose, kitoje aukštos rizikos grupės pacientams 39 proc. atvejų nustatyta išeminė širdies liga, o kalcio indeksas 0 Agatstono vienetų.

Visos 4 studijos (viena iš jų metaanalizė), analizavusios vainikinių arterijų KT angiografijos skubios pagalbos skyriuje vertę, esant krūtinės ląstos skausmui ir žemai – vidutinei rizikai, patvirtino

reikšmingą jos sąlygotą laiko iki diagnozės nustatymo sutrumpėjimą, ūmių koronarinių įvykių sumažėjimą bei retesnį pakartotinų vizitų dažnį. Šiose studijose gauta aukšta diagnostinė vainikinių arterijų KT angiografijos vertė, jautrumas buvo 86-100 proc., neigiama prognostinė vertė 93-100

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6 vaizdų kokybė reikšmingai nesiskyrė nuo vainikinių arterijų KT angiografijos tyrimo (OR = 0.78, 95%

CI = 0.58 to 1.06; I2 = 0%), tačiau trigubo atmetimo tyrimas buvo susijęs su didesne apšvita.

Išvados: Kalcio kiekio tyrimas pasižymi aukšta neigiama prognostine verte besimptomiams pacientams, tačiau ūmaus krūtinės skausmo atveju kol kas vienareikšmių rekomendacijų nėra, nes simtpomus gali sąlygoti nekalcifikuotos plokštelės; vainikinių arterijų KT angiografija reikšmingai sutrumpina laiką iki diagnozės nustatymo bei sumažina paciento gydymo išlaidas, pasižymi aukštu jautrumu ir neigiama prognostine verte; trigubo atmetimo tyrimas yra universalesnis, tačiau techniškai sudėtingiau atliekamas, susijęs su didesne apšvita, todėl turėtų būti taikomas pacientas su nespecifine klinika

Raktiniai žodžiai: Širdies KT; Trigubo atmetimo tyrimas skubios pagalbos skyriuje; Ūmus krūtinės ląstos skausmas; Kalcio indekso tyrimas skubios pagalbos skyriuje; Vainikinių arterijų KT

angiografija skubios pagalbos skyriuje

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ACKNOWLEDGMENTS

I would like to express my sincerest gratitude to my lovely mother, father, brothers, and sister Dr. Sidra Malik, for their continuous encouragement and support.

I would also like to thank my friends, professors and university staff, without whom this thesis would not have been possible.

Last but not least, I would like to express a very special thank you to my brilliant supervisor, Dr. Antanas Jankauskas for sharing his guidance and expertise throughout this research project.

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CONFLICT OF INTEREST

The author reports no conflicts of interest.

ABBREVIATION

ACS – Acute coronary syndrome CAC – Coronary arteries Calcium CCT – Coronary computed tomography

CCTA – Coronary computed tomography angiography CT – Computed tomography

EBCT – Electron beam computed tomography ECG - Echocardiography

ECG – Electrocardiography ED – Emergency Department

ESC - European Society Of Cardiology ICCM - Iodine containing contrast medium MDCT - MULTIDETECTOR HELICAL CT

NICE - National Institute for Health and Care Excellence NPV - Negative predictive value

TRO CT – Triple rule out computed tomography

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CHAPTER 1: INTRODUCTION

Chest pain is among the most common reason for a patient to visit Emergency Department (ED). The challenge ED physicians faces is to accurately and efficiently identify the small proportion of patient with myocardial infarction or other life-threatening conditions. These challenges can lead to expanding of the logistic burden for emergency medical service ⁽¹⁾.

Acute chest pain is one of the common complains in the ED in Europe and the United States.

Among all 119 million visit every year, 6 million patient present with acute chest pain. These can be divided into low, moderate and high-risk patients. Up to 79 % of these patients fall into the low-risk category. Among low-risk patient, 5% have an acute coronary syndrome (ACS), compared with intermediate - risk 20% and 40 % with high – risk ^(2,3).

For the moment ED standard of care assessment for the low-risk chest pain patients often involves numbers of cardiac enzymes tests, serial echocardiography, and cardiac stress test. Such assessments can take up to 30 hours, and it is expensive. By implementing a new strategy of treatment could lead to a shorter length of stay and reduce the cost significantly as its shown in Fig. 1 ⁽³⁾.

The National Hospital Ambulatory Medical Care Survey in the United States has stated, the most common reason given by a adult patient (15 years above) for visiting the ED, in descending frequency: chest pain, abdominal pain, back pain, headache, and shortness of breath, with an estimated 6.4 millions visits ⁽³⁾.

An annually estimated cost of a patient with acute chest pain in ED exceeds $10 billion. Not all patients with acute chest pain have a life-threatening underlying condition. Although a significant proportion of these patients are unnecessarily admitted for observation, which puts additional strain on already limited resources ⁽³⁾.

One of the most clinically relevant conditions causing chest pain that have to be differentiated in the ED are pulmonary embolisms, acute aortic syndrome, and coronary artery disease presenting as ACS. ACS has been identified in approximately in 15-25% of patients with acute chest pain who are evaluated in EDs ⁽³⁾. It is unfortunate that the number of patients with a manifestation of acute myocardial infarction who are inappropriately discharged from ED is not negligible ⁽¹⁾. Undetected myocardial infarction is one of the most common reasons for litigation stemming from ED treatment and results in higher awards recovered in malpractice lawsuits in any other conditions ⁽³⁾.

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Figure 1.Three different temporal sequences of events that analyses of ED length of stay and charges.

AJR:193, July 2009 151

Coronary CT Angiography of Chest Pain

by these patients. The second and third analyses involved earlier discharge scenarios based on negative coronary CTA results.

Materials and Methods

This HIPAA-compliant study was approved by the university institutional review board. Writ- ten informed consent was obtained from each patient by a trained and experienced research associ- ate who recruited patients in this urban academic emergency department between the hours of 7:00 am and 6:00 pm, Monday through Friday. The consent allowed the addition of cardiac coronary CTA to the SOC workup and also allowed the research- ers access to electronic medical and billing records related to the emergency department visits.

Patients

Qualifying patients all had chest pain and a low TIMI risk score of 0–2. Patients were excluded if they had positive initial cardiac enzyme tests, new ischemic ECG changes, TIMI risk score greater than 2, known cardiac disease, or inability to achieve a heart rate below 75 beats per minute (bpm) with the use of β-blockers. Clinical exclu- sion criteria for coronary CTA included severe al- lergy to iodine-containing contrast material, history of compromised renal function (calculated glomerular filtration rate < 40 mL/min/1.73 m²), pregnancy, a nonsinus rhythm, severe respirato- ry or cardiac failure, women under the age of 45 years, men under the age of 30, or a body mass index (BMI) greater than 40. Between September 2006 and December 2007, we enrolled 53 sequen- tial patients who met these criteria.

Tests

At admission, as part of the SOC for chest pain, all patients underwent initial 12-lead ECG, a cardiac troponin I test, and chest radiography.

In addition, each patient also had blood labora- tory work and received drugs tailored to the presenting symptoms (Fig. 1). After the initial negative ECG and negative cardiac enzyme results were made available to the emergency department physician, in addition to the SOC, all patients consented to undergo 64-MDCT coronary CTA with retrospective ECG gating and tube current modulation or with prospective ECG triggering (LightSpeed VCT XT, GE Healthcare). Circu- lation time was determined with a timed bolus of 20 mL of iodixanol (Visipaque 320, GE Health- care). Contrast enhancement was achieved using a three-phase bolus (70 mL of iodixanol followed by 50 mL of a 70:30 blend of iodixanol and saline, followed by 50 mL of saline) injected at 5 mL/s. Coronary CTA was acquired with detector collimation of 64 × 0.625 mm at 0.625-mm incre-

ments and with a gantry rotation time of 0.35 second. A negative coronary CTA examination was defined as no greater than 30% luminal stenosis in any coronary artery segment as interpreted by two experienced reviewers working independently at separate times on a dedicated workstation (AW 4.4, GE Healthcare) [10]. One reviewer was a radiologist and one a cardiologist, both with 5 years’

experience with coronary CTA.

After the coronary CTA examination, patients were transferred to an emergency department observation unit, and SOC testing was continued, which included serial 12-lead ECG examinations and serial cardiac enzyme tests every 6 hours for 12 hours. After the negative results were available from this serial testing, the patient stayed in the observation unit until a stress test (^99mTc-tetrofosmin SPECT or stress echocardiography) was per-

formed as soon as possible during regular busi- ness hours (8:00 am to 5:00 pm).

Follow-Up

Forty-six patients were contacted by telephone 3 months after their emergency department visit, and 48 were contacted at 6 months. Using this combination, 49 of the 50 patients were contacted and questioned about evidence of subsequent major adverse cardiovascular events. One patient was lost to follow-up.

Data Collection and Processing

Test results and time course for this analysis were obtained from each patient’s electronic medical record. Patient admitting time, time of tests and results, and patient discharge times were all en- tered into the study database. All hospital charges

0:00 1:00 2:00 3:00 4:00 5:00 6:00 7:00 8:00 9:00 10:00 11:00 12:00

Length of Stay (h)

13:00 14:00 15:00 16:00 17:00 18:00 19:00 20:00 21:00 22:00 23:00 24:00

25:00 Discharge

Stress test results reported to emergency department physician Stress test

Last cardiac enzyme results available to emergency department physician Wait in observation unit for stress test

Patient presents with chest pain

Initial cardiac enzyme test Patient-specific labs Patient-specific drugs Chest radiograph Admit to observation unit Serial cardiac enzyme test/ECG Initial 12-lead ECG

Standard of Care

Last cardiac enzyme results available to emergency department physician Discharge

Initial cardiac enzymes Patient-specific labs Patient-specific drugs Chest radiograph

-blocker for CT scan CT scan

Initial 12-lead ECG

CT results made available to emergency department physician Admit to observation unit for serial ECG/enzyme tests Coronary CT Angiography

With Observation

Discharge

Initial cardiac enzymes Patient-specific labs Patient-specific drugs Chest radiograph

-blocker for CT Scan CT scan

Initial 12-lead ECG

CT results made available to emergency department physician Coronary CT Angiography

Without Observation

Fig. 1—Temporal sequence of events in three analyses of emergency department length of stay and charges.

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CHAPTER 2 AIM AND OBJECTIVE

AIM: To analyze and review the use of cardiac CT during acute chest pain in ED settings.

OBJECTIVE: To evaluate diagnostic value, advantages and disadvantages of calcium score in emergency settings, coronary CT angiography and triple rule out study in emergency settings.

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CHAPTER 3: LITERATURE REVIEW

NON – INVASIVE IMAGING IN CLINICAL CONTEXT

The challenge to the physician in ED is the quick identification of those patients with acute chest pain who requires admission and insistent management. Patients with low risk can be discharged from the ED. Despite this, it is possible to find patients with <5% possibility of myocardial infarction based on a simple clinical and ECG findings. It is essential that today's diagnostic method has to be more accurate as misdiagnoses carry a risk of severe adverse outcomes for the patients but also significant liability for doctors or the hospitals ⁽⁴⁾. In my review ill be focusing on non-invasive imaging tool to assess patients with acute chest pain in the emergency department.

ECHOCARDIOGRAPHY

The existing European Society Of Cardiology (ESC) guidelines on ACS put particular emphasis on the early utilization of echocardiography (ECG) in patients with acute chest pain . According to ESC among non – invasive imaging procedures, ECG is an essential modality in the acute situation because it is fast and usually available. Left ventricular systolic function is a necessary prognostic feature inpatient suspected with coronary artery disease and can be quickly assessed by ECG ⁽⁴⁾.

ECG has been utilized for diagnostic and risk assessment in patients presented to the ED with symptoms that could suggest CAS on the basis of its high degree of consistency in identifying regional wall motion abnormalities ⁽⁴⁾.

Echocardiography is one of the most common and cost-effective non-invasive imaging

techniques for the preliminary diagnosis in patients suffering from acute chest pain and possible ACS.

The site and the magnitude of ECG changes may provide vital prognostic information. Despite this, a substantial number of patients presenting to ED with acute chest pain, baseline echocardiography changes may be related to underlying pericarditis, left ventricular hypertrophy, left bundle branch block, and early repolarization leading to overdiagnosis and unnecessary admission for ACS. In spite of this, up to 40%-65% of patients with developing ACS have normal or inconclusive results. The reason behind lack of ischemic or diagnostic change can be smaller infarct, the timing of the ECG in relation to the onset of myocardial ischemia or necrosis, infarct site specifically in the distribution of left circumflex artery, and the degree of collateral circulation to the exposed myocardium ⁽⁵⁾.

In a study done by Pope et al.⁽⁵⁾, 10,689 patients were presented to ED with chest pain. Among them, 1 of the 4 had a normal or inconclusive ECG, and predictors of missed diagnosis and subsequent failure admit patient with cardiac ischemia or infarction ⁽⁵⁾. Consecutive ECGs have higher accuracy in

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diagnosing ACS as compared with a single ECG, in spite of this changes may take up to several hours to appear. This limits their negative prognostic value in ED ⁽⁵⁾.

CARDIAC BIOMARKERS

Cardiac biomarkers (troponin I and T) are structural proteins unique to the heart and are very sensitive and specific for myocardial damage. Several studies have shown that increased level of these markers in the blood in the patients with ACS is related to unfavorable outcomes. For a standard troponin assay, the sensitivity and specificity are usually as high as 99% and 86% respectively for detection of acute myocardial infarction in patients presenting with acute cardiac pain within 24 hours in ED ⁽⁵⁾. Majority of troponin assays are limited by their late peaking in the blood circulation, and for that reason, it requires serial monitoring over a period of 6-12 hours. In the first 3 hours of onset of symptoms for the detection of myocardial infarction or other major cardiac events, the sensitivity of cardiac troponin is poor. Beside negative troponin T or CK-MB does not necessarily present a low-risk complication in patients presenting with cardiac pain ⁽⁵⁾.

A study was done by McErlean et al.,⁽⁵⁾ reported 55% of patients presenting with chest pain, who eventually had an adverse in-hospital event, did not have a positive troponin test even up to 16 hours of hospital admission. Therefore a single negative cardiac biomarker test in ED should not be used as a reliable indicator to discharge patients presenting with chest pain. Compared to standard troponin assays, highly sensitive troponin assays have recently shown higher diagnostic accuracy for acute myocardial infarction. The negative prognostic value for highly sensitive troponin I, 3 hours after admission with acute chest pain was reported to be 99.6%, where the positive value reported to be 96.6% making it a useful method for both ruling out or confirming MI, respectively at 3 hours ⁽⁵⁾. In spite of high diagnostic accuracy or troponin determination for acute myocardial infarction, ACS may not be noticed due to its inability to identify myocardial ischemia without necrosis is. These

inconsistencies of traditional marker for ACS in a patient presenting with symptoms of chest pain in the ED have led to discussions of utilizing multiple imaging modalities to assess in early diagnosis, risk stratification, and avoidance of unnecessary admissions ⁽⁵⁾.

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14 NUCLEAR IMAGING

The effectiveness of rest radionuclide MPI with either technetium 99m – sestamibi or tetrofosmin in patients with chest pain is well validated. The unique characteristics of rest MPI can detect abnormal images at the very moment that regional myocardial blood flow is disturbed. The degree of perfusion defect correlates well with the anatomical size of myocardial ischemia. Rest MPI has shown to be useful to detect acute MI with a sensitivity of 90% and specificity of 80%, provided that imaging is completed within 6 hours of the onset of chest pain. Despite this, one single rest MPI one cannot distinguish between ACS and decreased regional blood flow due to previous infarction ⁽⁵⁾.

Checking the MPI in an ED setting has been proven to be a clear negative predictive value at an accuracy of greater than 99%. Successfully indicating that patients with an on-going chest pain show a relatively normal rest MPI, and thus is unlikely to have ACS. Along with being a good

diagnostic indicator, MPI can also give prognostic data in acute settings. Patients with normal rest MPI have low 30-day cardiac event rate, in comparison to patients with an abnormal rest MPI, who have an estimated 10–30% 30-day cardiac event rate ⁽⁵⁾.

CT TECHNOLOGY

There are many options available for clinicians for the non-invasive evaluation of acute chest pain ⁽⁶⁾. Cardiac Computed tomography is one of them. Over the last two decades, CT has evolved rapidly ⁽⁷⁾.

There are two types of CT scanner available for imaging the heart. The first one is an older

technology called electron beam CT (EBCT). The second one is multidetector helical CT (MDCT).

EBCT use an electron gun to generate electrons, which are then electromagnetically steered across a stationary tungsten anode. EBCT does give an excellent temporal resolution, but the spatial resolution is considerably less than that of MDCT, providing a notable decrease in the use of EBCT ⁽⁶⁾.

State - of - the - art MDCT scanners use rotating slip-ring gantries that can revolve around the patient 350 milliseconds or less. Since its only required a half rotation to generate tomograms, the heart can be imaged in 175 milliseconds or less ⁽⁶⁾. Imaging time with these scanners maybe less than 10 seconds when only the heart is evaluated and less than 20 when the entire thorax is scanned with ECG

synchronization. In the State – of – the –art MDCT scanners generation, obtaining motion free scans of the heart and thoracic, vascular structures within a reasonable breath hold time has become the feasible and enabled use of this technique in the ED ⁽³⁾.

64 - MDCT scanners acquire 64-320 cross – sections per rotation, depicting vascular details with a spatial resolution <0.5 mm ⁽⁷⁾.

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Limitation and concern related arrhythmias, high and variable heart rates, and extensive calcification, however, have motivated further refinement of CT technology, resulting in the

introduction of dual-source CT ⁽³⁾. These scanners use two radiation producing tubes and detectors at 90⁰, reducing temporal resolution further to approximately 83 milliseconds or less. Dual source CT makes it feasible to even perform a scan on patients with dysrhythmias, such as arterial fibrillation ⁽⁶⁾.

When imaging the heart, it`s necessary to synchronize the imaging process with the cardiac cycle. The two general techniques that can be utilized to accomplish this are prospective triggering and retrospective gating, which use an electrocardiogram for reference. The most optimal time to acquire images of the coronary arteries is diastole because the heart is nearly motionless. For ventricular function information, the entire cardiac cycle must be imaged ⁽⁶⁾.

With prospective gating technique, MDCT predicts the occurrence of diastole and turns on the X-Ray source after a preselected delay. The source of x-ray remains on for only a brief period and is turned off before the next QRS complex. This short x-ray pulse is sufficient to image the entire heart during a single heartbeat using the newer MDCT scanners. This technique can reduce the radiation exposure by up to 90% compared with retrospective gating ⁽⁶⁾.

With retrospective gating technique, the x-ray tube remains on throughout the entire cardiac cycle and for as many heartbeats as is required to image the entire heart. Once the scan is finished, images are reconstructed to represent any desired part of the cardiac cycle ⁽⁶⁾.

CORONARY ARTERY CALCIUM SCORING

EBCT primarily studied calcium artery calcium scoring. However multidetector computed tomography became the modality of choice for CAC evaluation. EBCT is now almost unavailable for CAC because of this. The establishing of the CAC score by CT is based on 3 mm axial slices without overlapping, and its limited to the cardiac region. This process is synchronized with ECG at a predetermined moment in the R-R interval, usually in the mid/late diastole without the use of contrast medium ⁽⁸⁾. The Society of Cardiovascular Computed Tomography recommends an effective radiation dose of 1,5mSv for this examination. Usually is less than that. Agatston method, determination of the volume of calcium, and determination of the mass calcium score are the primary system of the quantification of the CAC score. The first two are most communally used ⁽⁸⁾.

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16 CORONARY ARTERY CALCIUM SCORE IN ED

Coronary artery calcium has been used as an alternative approach for stratification of global cardiac risk, evaluation of acute chest pain patients and prediction of future cardiac events. The primary imaging modalities for CAC quantification are EBCT and CCT ⁽⁹⁾. Both technologies give thin slice computed tomographic imaging. While CCT has higher spatial resolution and lower hardware costs, the EBCT moves the X-ray source point electrically providing faster acquisitions ⁽⁹⁾. The calcifications of coronary arteries are defined based on X-ray attenuation as hyper – attenuating lesions >130 Hounsfield Units. The most established and widely used method to quantify CAC is the Agatston score. Agatson score is determined by calcified lesion area and calcium density factors.

There are other measurements, which are not routinely used in clinical practice, such as the calcium volume score and calcium mass or recently, lesions and vessel – specific CAC score ⁽⁹⁾.

At this moment, there are no published guidelines for the use of CAC score in the assessment of acute chest in ED. Appropriate use criteria of CCT been reported to help clinicians with proper patient selection criteria and avoid overuse. By these recommendations, the use of CAC and CCT should be restricted to patients at low ton intermediate cardiac risk (overall TIMI score 4 as shown in table 1) whose first set of cardiac biomarkers and initial ECG results show no sign of acute myocardial ischemia ⁽¹⁰⁾. The American Heart Association suggested to, that use of CAC score might be

recommended in intermediate risk patients to improve cardiovascular risk assessment (Class IIb) as well as in chest pain patients with negative cardiac biomarkers and equivocal or normal ECG. For patients with a built up CAD, CAC has poor specificity in the acute setting, and hence, diagnostic and prognostic incentive in this population, and for that reason it remains controversial, limiting its use across the board. Instead of CCT, atrial fibrillation, corpulence or renal inadequacy are not rejection criteria to performing CAC scoring because there is no requirement for contrast agents and the post- preparing investigation is not restricted by the presence of arrhythmias ⁽¹⁰⁾.

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Table 1. Thrombosis in Myocardial Infarction (TIMI) risk score

ADVANTAGE AND LIMITATION OF CAC SCORE IN THE ED

CAC scoring seems to provide essential data for initial risk stratification of the ED acute chest pain patient. A few favorable circumstances incorporate its non-invasive nature with an NPV (negative predictive value) that is similar to stress testing. Unlike other functional investigations, it isn't

constrained by simultaneous medicines, the patient's capacity to exercise, or baseline wall movement or abnormal findings on ECG. Also, there is no requirement for iodinated contrast media, particular patient arrangement or collaboration. CAC scoring is inexpensive, faster, less demanding to perform and more accessible than other imaging systems with low radiation measurements. Another potential favorable position over functional studies investigations is the ability to detect coronary calcium in non-obstructive lessons, giving the chance to start restorative treatment in the beginning times of non- obstructive atherosclerotic disease that by definition would not be found by conventional pressure testing ⁽¹⁰⁾.

In diabetic patients, the CAC score provides great help to identify individuals most at risk, could have an advantage from screening for silent ischemia and from more aggressive clinical treatment ⁽⁸⁾.

A study (ROMICAT) showed only 1 patient out of 197, had a 0 CAC score and presented with signs of an attack that was of cardiac nature, during the 6-month check up ⁽¹¹⁾. Another study Laudon et al. ⁽¹²⁾ analyzed 263 patients complaining of chest pain with a low to intermediate risk, and

ultimately established that with no CAC, the risk for myocardial ischemia is extremely low. Therefore,

Coronary CT and the Coronary Calcium Score Current Cardiology Reviews, 2012, Vol. 8, No. 2 87

mon clinical decision instrument utilized in the ambulatory care setting is the Framingham multivariable score system (FRS). This score, which is comprised of multiple clinical variables, is used to predict the 10 year risk of coronary heart disease (including coronary death, myocardial infarction and angina) [12]. The risk of suffering an adverse cardiac event is classified as low, moderate or high, when the predicted risk is less than 10%, between 10% and 20% or greater than 20% respectively [13]. Although useful for the longitudinal long term management of patients in the ambulatory setting, the sensitivity and negative predictive value provided by the FRS is not adequate to meaningly inform disposition decisions in the ED. (PROCAM score) [14, 15].

Similarly, risk scales have been developed to stratify in- dividual short term cardiovascular risk according to clinical presentation, ECG and cardiac biomarkers. One widely used score is the thrombolysis in myocardial infarction (TIMI) risk score (Table 1). This seven point scale classifies the target population into 3 groups based on their 14 day risk of adverse cardiac events: high risk patients (TIMI risk 5-7), who are commonly referred for urgent coronary angiography, intermediate (TIMI score 3-4) and low risk (TIMI score 0-2) patients who generally undergo a period of observation and serial biomarker testing followed by a risk stratification study of some type [16]. To help facilitate this process, so called chest pain observation units have become common- place in many tertiary care centers. These units typically provide a standardized approach to the evaluation of acute chest pain that combines information from serial ECG, cardiac biomarkers, and stress testing, allowing an expedited, protocoled cardiac evaluation without the time or expense of an in-patient stay.

CORONARY CALCIUM SCORE IN THE EVALUA- TION OF ACUTE CHEST PAIN IN THE ED

The CAC score has been proposed as an alternate approach for stratification of global cardiac risk, evaluation of chest pain patients and prediction of future cardiac events.

Electron-beam computed tomography (EBCT) and CCT are the primary imaging modalities for CAC quantification. Both technologies employ thin axial slice computed tomographic imaging. While EBCT moves the X-ray source point electri-

cally providing faster acquisitions, the CCT has higher spatial resolution and lower hardware costs. Coronary artery calcification is defined based on X-ray attenuation as hyper- attenuating lesions >130 Hounsfield Units. The most widely used and established method to quantify CAC is the Agatson score which is determined by calcified lesion area and a calcium density factor [17]. Other measurements, such as the calcium volume score and calcium mass or more recently, lesion and vessel-specific CAC score, are not routinely used in clinical practice. However, the calcium volume score seems to better reflect increases in plaque size and reduce variability between scans [18].The total score corresponds to the sum of all lesions in all three coronary arteries, and is commonly expressed in age and gender specific threshold values to improve diagnostic accuracy.

Evidence Base: CAC Quantification and Relation with Cardiovascular Events

CAC is a quantifiable marker of atherosclerotic disease [17] which correlates well with histological, intracoronary ultrasound and angiographic measures of coronary plaque burden [19, 20]. Furthermore, CAC score is an established predictor of cardiovascular events [21- 23]. However, the role of CAC score as part of the initial evaluation of patients in the acute setting remains controversial.

Over a decade ago, McLaughlin et al. [24] demonstrated the usefulness of CAC score in this scenario when they evaluated 134 patients with acute chest pain and a normal or non-diagnostic ECG. The prevalence of the presence of CAC in this study was 64%. The authors concluded that patients with CAC score of 0 could be safely discharged based on a demonstrated NPV of 98%. Similarly, Laudon et al. [25]

suggested that no further testing was needed in the cases of zero CAC score after studying 105 patients with acute chest pain, normal biomarkers and non-diagnostic ECG’s with several testing modalities, including EBCT scanning, exercise ECG testing, conventional coronary angiography, radionuclide stress testing and echocardiography. Accordingly, Sarwar et al. [26], based on a NPV of 93% from a systematic review of 18 studies, argued that patients with a CAC score of 0 are highly unlikely to have CAD and do not need further testing. More recently, Fernandez-Friera et al [27] found Table 1. Thrombosis in Myocardial Infarction (TIMI) Risk Score

Risk Factors

- Age > 65 years

- History of known coronary artery disease (>50%)

- Severe angina symptoms (>2 episodes of chest pain in the last 24 hours)

- ST-segment deviation on admission ECG (persistent depression or transient elevation) - Elevated serum cardiac biomarkers (troponins)

- Use of aspirin in the last 7 days before presentation

- 3 or more cardiac risk factors (age, male sex, family history, hyperlipidemia, diabetes, smoking, obesity) Low risk= 0-2 points; Intermediate risk= 3-4 points; High risk= 5-7 points. Each positive factor is worth it one point.

(18)

18 investigation and for that reason should be followed by additional diagnostic imaging investigations.

Moreover, because the vessel lumen isn't visualized and this test can't measure the severity of the coronary artery stenosis, however, elevated amounts of CAC are identified as an increased probability of obstructive CAD ⁽⁹⁾. Another restriction is that the presence and severity of non-calcified plaques can't be assessed by this examination, overlooking so-called "soft" plaques that can harm the vessel leading to rupture or thrombosis ⁽⁹⁾.

Conversely, other studies propose a lower diagnostic utility. The study by Rubinstein et al. ⁽¹³⁾ found a substantial occurrence of CAD in patients with no CAC (7%) and with a low CAC score (17%). A study included high-risk patients; with 5 out of 13 (39%) patients who had a CAC score of 0 also had severe CAD. (The incidence of CAD was approximately 70% in this study ⁽¹⁴⁾. Another study by the Gottlieb group ⁽¹⁵⁾ determined that 12% of patients who arrived for elective coronary

angiography with non-CAC vessels had severe CAD. The studies as mentioned earlier were carried out in a clinical setting with a very high prevalence of severe CAD (56%-70%), and consequently, the NPV given by a CAC score was lower. Numerous studies carried out by numerous centers stated the use of CAC score as a diagnostic method for obstructive CAD in symptomatic patients. The overall sensitivity and specificity was 95% and 66%, for CAC to calculate obstructive CAD using invasive angiography. ^(15,16)

CT CORONARY ANGIOGRAPHY

Coronary CT angiography has developed over the last 15 years as a non-invasive technique to assess the condition of the coronary arteries, cardiac chambers, and valves. The utilization of ECG gating permits synchronization of information acquisition to the cardiac cycle to minimize movement of the coronary arteries and cardiovascular structures ⁽¹⁷⁾.

Liquid agents, sometimes called Iodine containing contrast medium (ICCM) are injected into the veins. These agents increase the density of the blood in the vessels, allowing a better view on the angiogram of the blood vessel structures. Sometimes it hard to get clear images due to increased heart rate. To slow down the heart rate, medications are used ⁽¹⁷⁾.

COMPARISONS BETWEEN CCTA AND STRESS TESTING

Indirect and indirect comparison between CCTA and stress testing, CCTA consistently revealed superior diagnostic results when diagnosing coronary artery disease as defined by standard definitions. The difference in diagnostic performance has shown to be much clearer in sensitivity than specificity. Checking the non-obstructive CAD by CCTA in comparison to stress testing is beneficial as it allows for preventative and precautionary measures to be taken in order to

(19)

reduce any potential consequences. Available studies have indicated for CCTA to show better diagnostic and prognostic evidence in patients with suspected CAD compared to stress testing, but it remains doubtful if such evidence can lead to improved outcomes ^(18,19). Both positive and negative prognostic values are higher for CCTA compared to stress testing. As expected the results are indicative as CCTA is a test evaluating the coronary anatomy whereas the stress testing is for myocardial perfusion. However, recently the role of Fractional Flow Reserve as a more appropriate reference standard is being put forward with many arguing the measurement of fraction makes results more precise ^(19,20). In spite of this, recent practice guidelines in the US, and Europe continue to describe CAD according to anatomic criteria ^(19-21). This might be reasonable since there is a large body of evidence indicating great risk of adverse episodes in patients with an obstructive CAD, regardless of the disorder is correlated with hemodynamic changes or not ^(20,21).

In contrast to this, it should be noted that negative probability ratio for cardiac death and myocardial infarction related with normal CCTA is amazingly low and likely unmatched by stress testing when evaluating historical data. As expected given the incapability of stress testing to detect non-obstructive disease which is associated with adverse episodes. Based on such advantage for risk assessment, CCTA has shown assuring trends of improved patient outcome in the PROMISE, SCOT – HEART analysis and in the large CONFIRM registry despite the lack of certain treatment prescriptions ⁽¹⁸⁾.

ADVANTAGE AND LIMITATION OF CCTA IN THE ED

Early imaging in this setting guarantees to be an efficient, safe, and financially effective strategy for further risk assessments. In particular, CCTA allows a fast non-invasive investigation for the presence of coronary conduit ailment (CAD). The differential finding of no cardiac chest pain is really broad and includes life threating condition such as aortic dissection, pulmonary embolism, pneumothorax, pericardial tamponade, and mediastinitis. These may also be visible on CCTA ⁽²²⁾.

Numerous studies have shown the safety and efficiency of CCTA for the triage of patient presenting to the emergency department with thorax pain and a low to middle risk of ACS. These studies have shown CCTA to have a high sensitivity (86– 100%) and a high negative predictive value (93– 100%), in spite of the fact that the positive, productive value, utilizing invasive CCTA as a

(20)

20 facilitates discharge from the ED. This may help to lower costs compared with the usual protocol in appropriately selected patients (22,23,24,25).

The updated publication of the National Institute for Health and Care Excellence (NICE) Clinical Guideline 95 evaluates the performance and cost-utility of different non – invasive imaging strategies in patients suspected with acute chest pain. Because of the low cost and high sensitivity of CCT makes it first-line test for the assessment of stable coronary artery disease in chest pain pathways. Furthermore, randomized studies have demonstrated that CCT improves diagnostic certainty when combined with chest pain pathways ⁽²⁶⁾.

TRIPLE RULE OUT (TRO CT)

The differential diagnosis of acute chest pain is a complicated issue for the emergency physicians. The right decisions in patients suffering from acute chest pain remains a challenge. The patient's history, cardiac enzyme levels, or initial ECG often do not allow choosing the patients in whom additionally tests are required. Various vascular and non-vascular chest complications, such as pulmonary embolism, aortic dissection or ACS, as well as pulmonary and pleural pathology must be taken into consideration. TRO CT designates an ECG-gated protocol that allows detailed imaging of the pulmonary arteries, thoracic aorta and the coronary arteries within the single examination. This examination can be accomplished by utilizing dedicated contrast media administration regimen resulting in simultaneous attenuation of the three vascular territories. The utilization of the TRO CT examination for assessment of suspected ACS in the ED is possible because of advances in CT technology that provides more accurate z-axis coverage with improved resolution and decreased radiation dosage ^(26,27).

Triple rule out CT angiography can give a cost-effective assessment of the coronary arteries, aorta and pulmonary arteries and close lying intrathoracic structures for the patients with acute chest pain. Triple rule out is most appropriate for the patient who is considered to be at low to intermediate risk for acute ACS and whose symptoms may also be pointing towards pathology of the aorta and pulmonary arteries ⁽²⁷⁾.

Many studies have shown great to incredible diagnostic accuracy of dedicated CCAT for evaluation of coronary disease, with excellent negative values. Among these studies, only a few have described the application of computed tomography as part of TRO CT examination with a dedicated TRO injection an imaging protocol. A current survey of radiology practices found that 33% utilized CT in the ED for the workup of chest pain and that 18% were using a TRO convention ⁽²⁷⁾.

(21)

Three randomized large multicenter trials have shown that assessment in the ED is facilitated by CCTA scans to identify correctly. The reasons for acute chest pain and to acknowledge safe and rapid discharge after life-threatening conditions have been excluded ⁽²⁸⁾.

Figure 2.Example of TRO study performed in Lithuanian University Hospital Kaunas Clinics On the left 3 D reconstruction of heart and large vessels in thorax; on the right axial slice at the mid- thoracic level, where high-grade LAD stenosis and embolus in left lower lobar pulmonary artery simultaneously are visible.

ADVANTAGE AND LIMITATION OF TRO CT IN THE ED

TRO CT simultaneously examines the coronary arteries, the thoracic aorta, and the pulmonary arteries. Compared with dedicated CCTA, TRO CT has more anatomic coverage including the

structures the carina, which leads to a higher radiation dose. Along with higher radiation dose, TRO CT requires a slightly higher intravenous contrast load to opacify both the right and left circulations.

These scans need more time for the radiologist to review them. TRO CT is believed to be beneficial in the assessment of patients with acute chest pain for whom additional diagnoses other than ACS are considered, such as aortic dissection and pulmonary embolism ^(27,28).

4 studies assessed the image quality of TRO CT compared to dedicated to CT (Figure 3) ^(29,230-

33). Image quality was not significantly different between the two groups (OR = 0.78, 95% CI = 0.58 to 1.06; I² = 0%) ⁽³³⁾.

(22)

22 Figure 3. Image qualityTRO CT versus dedicated CT method.

RADIATION EXPOSURE

CCTA, SPECT, and CCT all expose patients to radiation. The dosage of retrospective gated 64 – slice CT typically ranges from 7 to 14 mSv when dose modulation approaches are used. The

radiation exposure you get from gated 64 – slice CT is comparable to stress SPECT (9 to 12 mSv) and lower than a thallium myocardial perfusion scan (18 to 21 mSv), but it's higher than the effective radiation dose from invasive coronary angiography (5 to 7 mSv) ⁽³⁴⁾.

A model-based controls indicated that lifetime cancer risk from standard CCT imaging differs from 1 in 143 (0.007%) for a 20 years old woman to 1 in 3261 for an 80 years old man (0.0001), with expressively lower risk when using dose modulation (1 in 715 and 1 in 1911, for a 60 years old women and men ⁽³³⁾.

In contrast to this, women in the US have shown to have a much higher risk, with a 12.5% lifetime chance of developing invasive breast cancer. The risk decreases with the overall cancer risk for 75-year-old men/women dropping to 6%. Despite the model-based assumptions for the cardiac CT related cancer risk and the estimations of the risk appearing low, we cannot disregard them. Furthermore, new data using prospective ECG gating is showing that some scan options (<5 mSv) could be used in its place to image-selected populations of ED patients while exposing them to a much lower dose of radiation ^(20,34).

EFFECT ON RESOURCE UTILIZATION

Emergency departments face difficulties identifying which patient to admit and which patient to discharge. Of the patient presented with acute chest pain to the emergency department, only 55-58

Table 4

Summary of the QUADAS-2 Assessment

First Author:

Reference No. Year

Risk of Bias Applicability Concerns

Patient Selection

Index Test

Reference Standard

Flow and Timing

Patient Selection

Index Test

Reference Standard

Johnson: 42 2007 Low Low Low High Low Low Low

Johnson: 19 2008 Low Low High High Low Low Low

Litmanovitch: 41 2008 High Low Low High High Low Low

Schuchlenz: 39 2010 Low Low High High Low Low Low

For flow and timing, all the studies are at high risk of bias because not all patients received the reference standard (only selected patients underwent coronary angiography).

QUADAS = Quality Assessment of Diagnostic Accuracy Studies.

Figure 2. Image quality: TRO CT versus dedicated CT scans. TRO = triple rule-out.

Table 5

Diagnostic Accuracy of TRO CT Compared to Invasive Coronary Angiography

First Author:

Reference No Year

Number of Coronary Segments Assessed

Sensitivity,

% (95% CI)

Specificity,

% (95% CI) LR+ (95% CI) LR– (95% CI) Schuchlenz: 39 2010 435 96.6 (90.3–99.3) 98.0 (95.9–99.2) 48.0 (23.0–100.0) 0.04 (0.01–0.11) Johnson: 19 2008 410 100.0 (78.2–100) 99.0 (97.4–99.7) 85.3 (33.9–214.5) 0.03 (0.00–0.48) Litmanovitch: 41 2008 130 81.0 (58.1–94.6) 92.7 (86.0–96.8) 11.0 (5.5–22.2) 0.21 (0.09–0.50) Johnson: 42 2007 20* 94.1 (71.3–99.9) 57.1 (18.4–90.1) 2.2 (0.9–5.2) 0.10 (0.01–0.77)

LR+ = positive likelihood ratio; LR– = negative likelihood ratio; TRO = triple rule-out.

*Diagnostic accuracy data were reported on a per-patient level rather than a per-coronary segment level.

Figure 3. Radiation exposure: CT versus control (values in mSv). TRO = triple rule-out.

ACADEMIC EMERGENCY MEDICINE • September 2013, Vol. 20, No. 9 • www.aemj.org 867

(23)

% do not have cardiac cause for their symptoms. Those who are admitted for acute chest pain, more than 60 % do not have ACS. Only in United States unnecessary admission alone cost billions of dollars annually ⁽³⁵⁾.

The standard diagnostic assessment for patients with acute chest pain may involve staying 8 hours in the emergency department before either discharge or admission. The emergency department is crowded because of prolonged and unnecessary hospitalizations resulting in bed shortages that can contribute to suboptimal resource utilization. By improving the ability to rule out, ACS could optimize the triage of chest pain as shown in Fig. 4 ⁽³⁴⁵.

Figure 4. Comparison between standard diagnostic and integrated diagnostic approach

A study from the United States showed the effect of CCTA on resource utilization showed good promise. Applying CCTA to the standard of care showed a change in diagnosis from ACS to

45 percent of patients.²² These data illustrate how CCTA can dramatically change resource utilization in both the emergency department and the hospital.

Similar changes in emergency department and hospital resource utilization were demonstrated in another study. Hospital length of stay and the percent of

Hospital length of stay was reduced by 8 percent (P = 0.049), and the percentage of unnecessary admissions was significantly reduced from 15 percent to 4 percent (P = 0.007), a 73 percent reduction.²⁶ CCTA has also been shown to affect diagnostic time and costs. It reduced initial diagnostic evaluation time from

$1,582 (P <0.001). Interestingly, patients evaluated by CCTA also had 3.5-fold fewer repeat evaluations for chest pain.²⁸ Thus, when CCTA is used in the diagnostic process, it can reduce unnecessary hospital admissions, change diagnosis, reduce diagnostic evaluation time, and lower diagnostic

Outlook

Chest pain patient

presents to the ED ECG tests

History/physical Coronary artery catheterization

Multiple cardiac troponin measurements

Risk

+

_

Intermediate High

Low High

Serial troponins Stress test (exercise or pharmacological)

Follow-up Serial ECGs

C L I N I C

+

_

Negative, no intervention

performed Positive, intervention

performed

Chest pain patient

presents to the ED ECG tests

History/physical Coronary artery catheterization

Multiple cardiac troponin measurements

Risk

+

? _

Intermediate High

Low High

Follow-up C L I N I C Additional evaluation^*

+

_

Negative, no intervention

performed Positive, intervention

performed

Traditional Chest Pain Triage Workflow: ~8–72 hours

Stress test (exercise or pharmacological)

_ +

Clinical suspicion still exists

Integrated Diagnostics Chest Pain Triage Workflow: ~4–12 hours

Additional evaluation^*

* May include MR and/or other diagnostic tests.

† Cardiac troponin measurements may be repeated as needed.

? ^CCTA^†

(24)

24 approach. Hospitalization length was decreased by 8% (P=0.049) and the percentage of unnecessary admission had drastically reduced from 15% to 4% (P=0.007), a 73% reduction ⁽³⁵⁾. The study did also confirm that CCTA has shown to affect diagnostics time and cost. It showed a reduction of diagnostic evaluation time from 15 hours to 3.4 hours (P<0.001), a threefold reduction. The cost was reduced by 16.5% from $1,872 to $1,582 (P<0.001) ⁽³⁵⁾. Remarkably, patient assessed by CCTA also had 3.5 fold fewer repeat evaluation for chest pain ⁽³⁵⁾. Through the reduction of the average diagnostic time from 12 to 4 hours and an associated reduction in costs from $4800 to $1200 per treatment, would cost

$1.95 million, this ultimately could save the hospital $5,85 million yearly ⁽³⁵⁾.

The facility of the combined diagnostics approach to providing better rule-out could help to reduce the demand to use more invasive procedures, like coronary catheterization for diagnosis. This might have a possible positive impact on patients and help to improve resource utilization ^(35,36,37).

(25)

CHAPTER 4 RESEARCH METHODOLOGY AND METHODS

Methodology: This was a Systematic Literature review where searches were conducted using several databases: Medline (PubMed), science direct publications and UpToDate. All articles

published from 2008 were included in the searches with no more than 10 years search criteria used.

The search terms used were: ‘cardiac CT,' ‘cardiac CT in the emergency setting,' ‘CT angiography in the emergency settings,' ‘calcium score in emergency settings,' ‘Triple rule out in emergency settings.' Keywords were matched to database indexing terms. In PubMed, the related articles were also

retrieved and added to this review.

Selection criteria: This review was conducted to investigate To evaluate diagnostic value, advantages and disadvantages of calcium score in emergency settings, coronary CT angiography and triple rule out study in emergency settings. Empirical studies were included; samples were taken from countries in Europe and the United States.

(26)

26

CHAPTER 5 RESULTS

The ROMICAT showed only 1 patient out of 197, had a 0 CAC score and presented with signs of an attack that was of cardiac nature, during the 6-month check up ⁽¹¹⁾. Another study analyzed 263 patients complaining of chest pain with a low to intermediate risk, and ultimately established that with no CAC, the risk for myocardial ischemia is extremely low.

Conversely, other studies propose a lower diagnostic utility. The Rubinstein study found a substantial occurrence of CAD in patients with no CAC (7%) and with a low CAC score (17%). A study included high-risk patients; with 5 out of 13 (39%) patients who had a CAC score of 0 also had severe CAD. (The incidence of CAD was approximately 70% in this study ⁽¹⁴⁾. Another study by the Gottlieb group ⁽¹⁵⁾ determined that 12% of patients who arrived for elective coronary angiography with non-CAC vessels had severe CAD. The studies as mentioned earlier were carried out in a clinical setting with a very high prevalence of severe CAD (56%-70%), and consequently, the NPV given by a CAC score was lower. Numerous studies carried out by numerous centers stated the use of CAC score as a diagnostic method for obstructive CAD in symptomatic patients. The overall sensitivity and specificity was 95% and 66%, for CAC to calculate obstructive CAD using invasive angiography.

(15,16)

Sarwar et al. 15 studies of CAC in acute coronary syndromes (ACS) presenting to the emergency room. CAC was absent in approximately 42% of patients, from which only 1% had an ACS translating to sensitivity and negative predictive value of 99% for CAC = 0 (6)

Another study included 1145 patients. Overall, 406 (35%) CCTA were normal, 454 (40%) had

<50% stenosis, and 285 (25%) had ≥50% stenosis. Among 483 (42%) patients with CAC zero, 395 (82%) had normal CCTA, 81 (17%) <50% stenosis, and 7 (1.5%) ≥ 50% stenosis. 2 (0.4%) patients had ≥70% stenosis ⁽³⁹⁾ .

Several studies with 3,539 patients (791 TRO and 2,748 non-TRO) were undertaken (1

randomized controlled trial and 10 observational). No significant difference was observed in the image quality between TRO and CT scans was seen. The TRO CT diagnostic accuracy estimates for CAD are: sensitivity at 94.3% (95%) confidence interval [CI] = 89.1% to 97.5%), specificity at 97.4% (95%

CI = 96.1% to 98.4%), the likelihood ratio for a positive result (LR+) given was 17.71 (95% CI = 3.92 to 79.96), and the likelihood ratio for a negative result (LR-) was 0.08 (95% CI = 0.02 to 0.27). The TRO CT method included more exposure to radiation (mean difference [MD] = 4.84 mSv, 95% CI = 1.65 to 8.04 mSv) and contrast exposure (MD = 38.0 mL, 95% CI = 28.1 to 48.0 mL) in comparison to patients that were not tested with TRO CT ⁽³³⁾.

(27)

Another study included 2068 patients (272 triple rule-out and1796 cardiac CT angiograms),the composite diagnostic yield was 14.3% with triple rule-out and 16.3% with cardiac CT (P 5 0.41) and was driven by the diagnosis of obstructive coronary artery disease (13.2% triple rule-out versus 16.1%

cardiac CT, P 5 0.22). The diagnostic yield for pulmonary embolism was low (1.1% triple rule-out and 0.2% cardiac CT, P 5 0.052) and no aortic dissections were found in either group. Compared with cardiac CT, the triple rule-out approach was associated with higher radiation exposure (12.0 6 5.6 mSv versus 8.2 6 4.0 mSv, P , 0.0001), a greater incidence of subsequent emergency center cardiac

evaluations (5.9% versus 2.5%, P 5 0.0017), and more downstream pulmonary embolism-protocol CT angiography (3.3% versus 0.9%, P 5 0.0034) ⁽³⁹⁾

In a different study obstructive CAD was found in 56 (19%) patients, of whom 42 (14%) underwent revascularization. CAC was zero in 131 (44%) patients, of whom two (1.5%) had obstructive CAD, and one (0.8%) underwent revascularization.

12,834 patients underwent computed tomography scanning (TRO,

n 1⁄4 1,555; coronary CTA, n 1⁄4 11,279). Diagnostic yield was similar TRO had higher median radiation (9.1 mSv vs. 6.2 mSv; p < 0.0001) and mean contrast (113 6 ml vs. 89 17 ml; p < 0.0001) doses. In emergency department patients, PE and AD were more often detected on TRO. Among inpatients, there were no differences in overall yield or in that of PE, AD, or CAD. ⁽⁴⁰⁾

The effect of CCTA on resource use showed great potential. Implementing CCTA to the standard of care changed diagnosis from ACS to Non-ACS in 44% of the patients and led to canceled hospitalization in 5% of the patients. The duration of admission in the hospital was decreased by 8%

(P00.049). The percentage of unnecessary admission was drastically reduced from 15% to 4%

(P=0.007) a 73 % reduction. Apart from this, CCTA has also shown to affect diagnostic time and cost.

It decreased the initial diagnostic evaluation time from 15 hours to 3.4 hours (P<0.001), which is a threefold reduction. The cost was reduced by 16.5 % from $1.872 to $1.582 (P<0.001). Remarkably, patient assessed by CCTA had 3.5 fold fewer repeat evaluation for chest pain ⁽³⁴⁾.

In another study the two CT-based earlier discharge was analysed, the CCTA resulted in a 54%

reduction in time to diagnosis compared with MPI (median 2.9 h [25th to 75th percentile: 2.1 to 4.0 h]

vs. 6.3 h [25th to 75th percentile: 4.2 to 19.0 h], p < 0.0001) ⁽¹⁾

Four RCTs and 3 case-control studies with 3306 patients undergoing CCTA and 2752 assigned to SOC were assessed. A significant reduction in the risk of ACS (RR: 0.26, 95% CI, 0.08 to 0.87; p =

(28)

28 Raggi et al. study shows the economic analysis of the 2 approaches revealed a cost reduction of over 65% when comparing the “CAC first” approach to that of exercise treadmill testing first ($599 vs.

$1701, average savings $1102 ± 123 [95% CI $860–$1344] ⁽³⁷⁾.

Results of 3 definitive randomized multicenter studies and real-world experience in a large health care system identified, a coronary CTA protocol as providing more efficient, less expensive, safe or safer than standard of care among patients who present to the ED with symptoms suggestive of ACS ⁽²⁵⁾

CONFLICT OF INTEREST

TABLE OF CONTENTS

SUMMARY

SANTRAUKA

ACKNOWLEDGMENTS

CONFLICT OF INTEREST

ABBREVIATION

CHAPTER 1: INTRODUCTION

CHAPTER 2 AIM AND OBJECTIVE

CHAPTER 3: LITERATURE REVIEW

CHAPTER 4 RESEARCH METHODOLOGY AND METHODS

CHAPTER 5 RESULTS