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SECTION V

CARDIAC IMAGING

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Chapter 40 Stress Perfusion CT Coronary Angiography: Expanding the Horizons SRIKANTH SOLA • PANKAJ M. KOLHE • SANJAYA VISWAMITRA

information that helps the clinician to determine whether any lesions that are present are haemody-namically signifi cant and lead to ischaemia. Unfor-tunately, functional imaging techniques suffer from limited sensitivity and specifi city (TMT), moderate accuracy which is worsened by poor echocardiogra-phy windows (stress echo), limited specifi city (SPECT) or high cost (PET). An ideal noninvasive diagnostic test would provide highly accurate ana-tomic and functional information.

Several CTCA-based approaches have been devel-oped which partially address this problem. CT frac-tional fl ow reserve (FFR) is highly accurate compared with invasive FFR 4–6 , but is limited by its high cost (US $800 per FFR study) and requirement for image data to be sent to a single US-based centre for analy-sis, with a delay of 1–2 working days. Transluminal attenuation gradient (TAG) analyses changes in the contrast enhancement across proximal and stenotic vessels to determine if a functionally signifi cant ste-nosis is present 7 , 8 . Unfortunately, TAG is available with a single vendor on 320-slice or higher scanners. Adenosine stress perfusion (ASP) CTCA combines the anatomic information of a CT image with func-tional data from a pharmacological stress perfusion study, and can be easily performed on most existing cardiac capable CT scanners at minimal additional cost. The result is a widely available noninvasive test with excellent sensitivity and superior specifi city 9 , 10 . In this chapter we will discuss the common indica-tions, techniques of acquisition and methods for evaluation of this new imaging modality.

INDICATIONS FOR ASP CTCA

Unlike conventional CTCA, for which multiple medical societies have developed Appropriate Use

INTRODUCTION

Computed tomography coronary angiography (CTCA) is a well-established noninvasive imaging modality for the evaluation of presence and severity of obstructive lesions in patients with intermediate likelihood of coronary artery disease (CAD) 1 , 2 . Diag-nostic accuracy with current-generation scanners is good, with sensitivity of 80%–90%, specifi city of 75%–85% and a negative predictive value of 99%.

Limitations that previously restricted the wide-spread adoption of CTCA, such as radiation dose, contrast dose, heart rate, atrial fi brillation and cal-cium, have been mitigated to various degrees by advances in technology. New dose-reduction tech-niques, for example, have reduced radiation expo-sure from CTCA considerably, with routine effective doses of �1 mSv or less possible in many cases. Similar reductions in contrast requirements have occurred, with contrast volumes of 40–50 mL, now the norm in most adult patients. Advanced scan-ners with dual source systems (two X-ray tubes) or wide detector coverage (�256 detectors) can cover the entire heart in a single rotation, allowing pa-tients with tachycardia or atrial fi brillation to be scanned with good diagnostic accuracy. Finally, dual-energy scanners can mitigate to some extent the effect of artefacts from calcifi ed arteries, reduc-ing the number of nondiagnostic studies.

Despite these advances, CTCA is often criticized in that it provides only anatomic information – whether coronary stenosis is present, and if so, how severe in terms of per cent diameter stenosis 3 . In comparison, other noninvasive modalities such as exercise treadmill testing (TMT), stress echocardiog-raphy, myocardial perfusion imaging and positron emission tomography (PET) provide functional

336 SECTION V — Cardiac Imaging

TABLE 40-1 CONTRAINDICATIONS TO ASP CTCA

• Serum creatinine level � 1.6 mg/dL and/or estimated glomerular fi ltration rate (eGFR) � 50 mL/min. This can be mitigated by performing rest and stress studies on two separate days, along with proper oral and/or intra-venous hydration before and after scan.

• Left ventricular ejection fraction (LVEF) � 40%. • Rhythm other than sinus. • Presence of arrhythmia, acute hypotension or clinically

unstable. • History of prior coronary artery bypass graft surgery, severe

pulmonary hypertension, congenital heart disease. • History of allergy to iodinated contrast materials. • Unable to achieve heart rate � 70 bpm (depending on

the scanner platform used) for the rest scan despite maximal tolerated doses of metoprolol and ivabradine.

• Unable to cooperate with breath hold for CTCA scan. • Unable to rest hands above head while supine (usually

due to frozen shoulder). • Contraindications to adenosine (signifi cant asthma or

reactive airway disease requiring continuous home oxy-gen, or prior intubation for respiratory failure; Mobitz type II second-degree AV block or greater on ECG).

• Contraindications to ivabradine (sick sinus syndrome, use of calcium channel blockers, use of antiretroviral medications, severe aortic insuffi ciency).

• Contraindication to metoprolol (systolic blood pres-sure � 100 mm Hg, Mobitz type II second-degree AV block or greater on ECG, severe aortic insuffi ciency).

• Contraindications to sublingual nitroglycerine (severe aortic stenosis, has taken sildenafi l, tadalafi l or any other phosphodiesterase inhibitor in last 48 h).

Criteria 11 , the indications for ASP CTCA are still evolving. The most common indications are as follows:

• To determine the functional signifi cance of a mod-erate (50%–69%) or severe (70%–99%) stenosis of an epicardial coronary artery seen on conventional CTCA.

• To determine the functional signifi cance of a heavily calcifi ed coronary artery stenosis. Con-ventional CTCA in such cases are generally non-diagnostic due to calcium blooming artefact.

• To evaluate coronary anatomy and ischaemia in a patient with known CAD but no prior revascu-larization.

ASP CTCA has several important contraindica-tions beyond those for conventional CTCA. These are related to the use of adenosine as well as in-creased iodinated contrast dose due to the require-ment for two contrast enhanced scans. The latter can be minimized by reducing contrast dose (par-ticularly on advanced contemporary scanners), or by acquiring the rest and stress scans on two differ-ent days. Additional important contraindications to ASP CTCA are listed in Table 40-1 .

IMAGE ACQUISITION

Patient preparation for ASP CTCA is similar to rou-tine CTCA studies, with the additional requirement of an extra peripheral IV line for administration of intravenous adenosine ( Table 40-2 ). This second line is placed in the antecubital fossa or hand opposite the IV that will be used for contrast administration.

The entire study is done in two steps, both of which are done in either single energy or dual-energy mode, depending on the particular scanner being used ( Fig. 40-1 ). In this chapter we focus on static or fi rst pass acquisitions, as this method when compared to dynamic acquisitions has been more extensively investigated, reduces radiation dose and is more accurate. A time difference of 10–20 min is maintained between the rest and the stress scans to avoid contrast contamination.

• First scan: Prospectively gated rest scan – routine CTCA study. Sublingual nitroglycerin is given before scan acquisition to improve visualization of the coronary arteries. ECG padding is kept at 80–100 ms to allow for evaluation of additional phases if needed.

• Second scan: Prospectively gated stress scan. Dur-ing pharmacologic vasodilator stress with ade-nosine, the stress scan is acquired. ECG padding

TABLE 40-2 PATIENT PREPARATION FOR ASP CTCA

• Patients should refrain from vasodilator medications or foods which interfere with adenosine for the previous 48 h, such as caffeinated beverages, chocolates and deriphylline.

• Patients should refrain from medications which interfere with sublingual nitroglycerin, such as sildenafi l and other phosphodiesterase inhibitors, for the previous 48 h, as well as from smoking, caffeine beverages and chocolates.

• Oral ivabradine plus oral and/or intravenous metoprolol can be used to reduce heart rate to �65 bpm as toler-ated by blood pressure (to keep systolic blood pressure � 100 mm Hg).

• A fasting state of at least 4 h is essential to avoid the risk of aspiration in cases of contrast reaction, which is a rare phenomenon.

• Two IV lines in separate arms, one each for contrast injection and adenosine infusion.

• Other minor preparation such as removal of any metal objects from scan fi eld of view, a loose gown, shaving of chest in men for better contact of ECG leads, etc.

337Chapter 40 — Stress Perfusion CT Coronary Angiography: Expanding the Horizons

is typically turned off to reduce radiation dose. Sublingual nitroclycerin is not given, as the stress scan focuses only on myocardial perfusion. Other scan parameters (tube voltage, tube current, slice thickness, etc.) remain unchanged.

At our centre we prefer to perform the rest scan fi rst, followed by the stress scan, as this allows the physician to quickly review the preliminary data and cancel the adenosine stress study if no potentially signifi cant stenosis is present. Patient cooperation with breath holding also tends to be better with the fi rst scan, thereby reducing respiratory motion arte-facts. A potential disadvantage of the ‘rest scan fi rst’ approach is the theoretical concern of contrast con-tamination in the second study in infarcted or fi brotic myocardium. This effect can be minimized by main-taining a gap of 10–20 min between the two scans, and by the use of dual-energy CT (discussed below).

Adenosine protocol: For the stress scan, adenos-ine is the preferred vasodilator. It is infused intra-venously through a separate IV line at a dose of 140 mcg/kg/min over 3 min. The stress produced typically produces an increase in heart rate of at least 10 bpm above the baseline. If the heart rate fails to increase with this dose, the adenosine dose is increased to 180 mcg/kg/min and then to 210 mcg/kg/min as required. Some patients may not demonstrate an increase in heart rate with adenosine, however, due to prior use of beta blockers and ivabradine. Scan acquisition is performed during the last minute of adenosine

infusion. Heart rate, blood pressure, cardiac rhythm and symptoms are continuously moni-tored during the procedure. Regadenoson is an adenosine analogue that has the advantage of requiring only a single injec-tion, but is currently not yet available for use in most South Asian countries.

Contrast dosing: Contrast dose used is typically 0.75– 1 mL/kg for the rest scan and 0.75 mL/kg for the stress scan, depending on the scanner used. Contrast quantity, rate of infusion and saline chase vary depending on the particular scanner being used. Typical contrast dose for an average 70-kg adult male (including timing bolus of 20 mL) is approximately 100–140 mL. An iso-osmolar contrast agent is therefore preferred due to the high-contrast dose. This contrast load represents the single major disadvantage of ASP CTCA.

Radiation concerns: Contemporary radiation dose management practices have minimized the effective dose from CTCA considerably, and these should be utilized to the extent possible. To fur-ther minimize radiation dose, a calcium scoring scan is not done (as these patients generally have known CAD) and ECG padding is turned off for the stress perfusion scan. Typical effective dose for ASP CTCA (depending on the scanner type and patient gender/body habitus) is between 2.5 and 6 mSv, which is considered as a low risk scan according to American College of Radiology (ACR) CT guidelines 8 .

IMAGE POSTPROCESING

Analysis of both rest and stress images for myocar-dial perfusion requires additional postprocessing, which can be done in several steps: segmentation of the left ventricular (LV) myocardium; segmentation of the heart into standard views for perfusion imag-ing; postprocessing; image interpretation. These steps are described in detail below.

Segmentation of the LV myocardium: The LV myocardium should be extracted using the myo-cardial perfusion package available on the work-station, and any necessary corrections to endo-cardial and epicardial contours made manually. Whereas the 17-segment model recommended by the American Heart Association 12 is commonly used for SPECT and PET images, the apical seg-ment on ASP CTCA is often limited by either beam hardening artefact (particularly on scanners without dual-energy mode) or by its inherent thin wall. For these reasons, most practitioners

Rest CTCA scan

10–20 minute interval and start of adenosine infusion

Stress CTCA scan

• At the end of 7th min, start Adenosine infusion over 3 min• Adenosine dose is 140 mcg/kg/min and can be increased

as required (180, 210 mcg/kg/min) to achieve heart rateincrease >10 bpm (not all patients will achieve this due to effects of rate controlling drugs)

• Proceed to stress scan after 10 bpm increase in HR orat end of the infusion protocol, whichever is early.

• Regular DECT coronary angiography• ECG padding ON per institutional protocol• No calcium scoring• For coronary anatomy and rest myocardial perfusion

• ECG padding OFF; no sublingual nitroglycerin• For stress myocardial perfusion

Figure 40-1. Flow diagram of acquisition protocol for an ASP CTCA study.

338 SECTION V — Cardiac Imaging

prefer to use a 16-segment model for evaluation of myocardial perfusion.

Segmentation of the heart into standard views: Both the stress and rest images should be divided into standard horizontal long axis (four-chamber), vertical long axis (two-chamber), three-chamber and short axis stack. The short axis views can be divided into either basal, mid and apical short axis segments or a series of short axis slices extending from the base to the apex, based on personal preference. With the former ap-proach, a 16-, 17- or 18-segment model can be used. In our experience, the apical segment is dif-fi cult to evaluate for perfusion defects due to the tendency for most segmentation software to seg-ment this slice rather thinly; accordingly we have adopted the 16-segment model. Care should be taken to ensure that the same anatomic planes are used for both stress and rest images.

Postprocessing: The most important part of im-age preparation for ASP CTCA, proper postpro-cessing, can simplify interpretation, minimize artefacts and avoid errors in interpretation due to improperly processed images. We recommend that minimum intensity projections with slice thickness of at least 2 mm be used, with a proper colour scale and window levels. Unfortunately, there is currently no standard for colour scales or window levels for ASP CT images, and settings are often vendor and platform specifi c.

IMAGE INTERPRETATION

Resting CTCA images should be reviewed for coro-nary anatomy in the usual manner, i.e. on a work-station with dedicated cardiac CT software in accor-dance with guidelines of the Society for Cardiovascular Computed Tomography (SCCT) 13 . In general, these require a combination of axial source images, maximum intensity projections, curved and straight multiplanar reformation and volume-ren-dered images.

Stress and rest perfusion images are compared side by side, often with the stress image above and rest image below, following the convention used by nu-clear cardiology. Hypo-attenuated areas of myocar-dium represent areas of reduced myocardial perfu-sion or reduced intravascular blood volume. Interpretation of stress and rest images are similar to that used for nuclear cardiology, with a few caveats as described below.

• A perfusion defect that is present at stress and reverses with rest is a reversible defect , and is

consistent with ischaemia ( Fig. 40-2 ). At least two contiguous segments or �12% of myocardial mass must be ischaemia for clinically signifi cant ischaemia to be present. These lesions are clini-cally managed with revascularization, either per-cutaneously or with coronary artery bypass graft-ing depending on the anatomy.

• A perfusion defect that is unchanged at both stress and rest is a fi xed defect , and is consis-tent with prior infarction. These segments are nonischaemic and clinically are managed medically.

• A perfusion defect that is present at stress and par-tially reverses with rest is handled differently. If the majority of the defect reverses with rest, then it is a partially reversible defect and usually indi-cates prior infarction with some degree of isch-aemia ( Fig. 40-2 ). If the majority of the defect remains fi xed with rest, then it is a partially fi xed defect (or predominantly fi xed defect) and indicates a lesser degree of ischaemia. Unfor-tunately, there are no studies to date to provide guidance on how to diagnose or determine sub-sequent clinical management for these partially reversed or fi xed defects.

The most common artefact that is specifi c to ASP CTCA is beam hardening in the basal inferior and apical segments. These can lead to false-positive results and reduced specifi city. However, these arte-facts are avoided by using dual-energy acquisitions where available.

Dual-energy ASP CTCA: ASP CTCA per-formed on dual-energy scanners require slight modifications in interpretation, especially when the stress scan is performed after the rest study. In such cases, iodine can accumulate in areas of infarction or fibrosis due to delayed wash in/wash out (similar to late gadolinium enhance-ment by MRI) resulting an area of high attenua-tion in infarcted segments on the stress and rest scans. Unlike conventional ASP CTCA, perfusion using dual energy is evaluated through colour-coded iodine maps generated, based on iodine content in myocardium allowing the quantita-tive assessment of perfusion.

CONCLUSION

ASP CTCA is a rapidly growing noninvasive modal-ity that offers both anatomic and functional infor-mation with a high degree of accuracy compared to invasive FFR. Advances in scanner technology per-mit low radiation and contrast dose. Dual-energy

339Chapter 40 — Stress Perfusion CT Coronary Angiography: Expanding the Horizons

LAD

A B

Ostial LAD

C

Mid LAD

Mid Ramus

Figure 40-2. Reversible perfusion defect indicating ischaemia in the LAD territory. A 57-year-old male ex-smoker with hypertension presented with class II exertional angina. An exercise treadmill test was nondiagnostic. Echo showed minimal hypokinesis in the anterior wall, with overall normal systolic function. (A) On the curved multiplanar reformatted image from the rest CTCA, the ostial left anterior descending (LAD, yellow arrow) had focal severe stenosis (70%–99%); the ostial D1 (white arrow) focal severe stenosis (70%–99%). A moderate sized ramus intermedius had proximal focal mild stenosis (25%–49%), whereas the left circumfl ex and right coro-nary artery had proximal minimal stenoses (�25%, not shown). (B) Stress (top) and rest (bottom) perfusion images in the basal to distal short axis levels showed partially reversible perfusion defects in the basal to distal anterior segments (red arrows), consistent with prior infarction with some degree of ischaemia. In addition, reversible perfusion defects were present in the basal to distal anteroseptal and basal to distal inferoseptal segments (yellow arrows), consistent with ischaemia. (C) Corresponding coronary angiogram of the left coronary artery demonstrating ostial LAD focal 80% stenosis, and mid LAD 70% stenosis. The patient underwent successful angioplasty and stent to the LAD.

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