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SECTION 1 Pathophysiology and investigation ofcoronary artery disease38

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cardiac surgery. 4th ed. Oxford:Blackwell Publishing Ltd, 2013, pp. 715– 43.

15. Poynter J, Williams W, McIntyre S, Brothers J, Jacobs M, Congenital Heart Surgeons Society AAOCA Working Group. Anomalous aortic origin of a coronary artery:a report from the Congenital Heart Surgeons Society Registry. World J Pediatr Congenit Heart Surg. 2014;5(1):22– 30.

16. Basso C, Maron BJ, Corrado D, iene G. Clinical prole of congenital coronary artery anomalies with origin from the wrong aortic sinus leading to sudden death in young competitive athletes. J Am Coll Cardiol. 2000;35(6):1493– 501.

17. Maron BJ, ompson PD, Ackerman MJ, Balady G, Berger S, Cohen D, etal. Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes:2007 update:a scientic statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism:endorsed by the American College of Cardiology Foundation. Circulation. 2007;115(12):1643– 55.

18. Jacobs ML. Anomalous aortic origin of a coronary artery:the gaps and the guidelines. J orac Cardiovasc Surg. 2017;153(6):1462– 5.

19. Erez E, Tam VKH, Doublin NA, Stakes J. Anomalous coronary artery with aortic origin and course between the great arteries:improved diagnosis, anatomic ndings, and surgical treatment. Ann orac Surg. 2006;82(3):973– 7.

20. Lee S, Uppu SC, Lytrivi ID, Sanz J, Weigand J, Geiger MK, etal. Utility of multimodality imaging in the morphologic characterization of anomalous aortic origin of a coronary artery. World J Pediatr Congenit Heart Surg. 2016;7(3):308– 17.

21. Jegatheeswaran A, Devlin PJ, McCrindle BW, Williams WG, Jacobs ML, Blackstone EH, etal. Anomalous aortic origin of a coronary artery (AAOCA):are we closer to risk stratication? American Association for oracic Surgery 98th Annual Meeting, 2018. San Diego, CA.

22. Cheezum MK, Liberthson RR, Shah NR, Villines TC, O’Gara PT, Landzberg MJ, etal. Anomalous aortic origin of a coronary artery from the inappropriate sinus of Valsalva. J Am Coll Cardiol. 2017;69(12):1592.

23. Brothers JA, Frommelt MA, Jaquiss RDB, Myerburg RJ, Fraser CD Jr, Tweddell JS. Expert consensus guidelines:anomalous aortic origin of a coronary artery. J orac Cardiovasc Surg. 2017;153(6):1440– 57.

24. Van Hare GF, Ackerman MJ, Evangelista JAK, Kovacs RJ, Myerburg RJ, Shafer KM, etal. Eligibility and disqualication recommendations for competitive athletes with cardiovascular abnormalities:Task Force 4:congenital heart disease. Circulation. 2015;132(22):e281.

25. Mery CM, De Leon LE, Molossi S, Sexson- Tejtel SK, Agrawal H, etal. Outcomes of surgical intervention for anomalous aortic origin of a coronary artery:a large contemporary prospective cohort study. J orac Cardiovasc Surg. 2018;155(1):305– 19.e304.

26. Lorber R, Srivastava S, Wilder TJ, McIntyre S, DeCampli WM, Williams WG, etal. Anomalous aortic origin of coronary arteries in the young:echocardiographic evaluation with surgical correlation. JACC Cardiovasc Imaging. 2015;8(11):1239– 49.

27. Fedoruk LM, Kern JA, Peeler BB, Kron IL. Anomalous origin of the right coronary artery:right internal thoracic artery to right

coronary artery bypass is not the answer. J orac Cardiovasc Surg. 2007;133(2):456– 60.

28. Mavroudis C. Coronary artery anomalies. In:Mavroudis C, Backer CL, eds. Atlas of pediatric cardiac surgery. London:Springer; 2015, pp. 359– 86.

29. Cubero A, Crespo A, Hamzeh G, Cortes A, Rivas D, Aramendi JI. Anomalous origin of right coronary artery from le coronary sinus— 13 cases treated with the reimplantation technique. World J Pediatr Congenit Heart Surg. 2017;8(3):315– 20.

30. Gulati R, Reddy VM, Culbertson C, Helton G, Suleman S, Reinhartz O, etal. Surgical management of coronary artery arising from the wrong coronary sinus, using standard and novel approaches. J orac Cardiovasc Surg. 2007;134(5):1171– 8.

31. Izumi K, Wilbring M, Stumpf J, Matschke K, Kappert U. Direct reimplantation as an alternative approach for treatment of anomalous aortic origin of the right coronary artery. Ann orac Surg. 2014;98(2):740– 2.

32. Mery CM, Lawrence SM, Krishnamurthy R, Sexson- Tejtel SK, Carberry KE, McKenzie ED, etal. Anomalous aortic origin of a coronary artery:toward a standardized approach. Semin orac Cardiovasc Surg. 2014;26(2):110– 22.

33. Gaudin R, Raisky O, Vouhe PR. Anomalous aortic origin of coronary arteries:‘anatomical’ surgical repair. Multimed Man Cardiothorac Surg. 2014;2014:mmt022.

34. Rodefeld MD, Culbertson CB, Rosenfeld HM, Hanley FL, ompson LD. Pulmonary artery translocation:a surgical option for complex anomalous coronary artery anatomy. Ann orac Surg. 2001;72(6):2150– 2.

35. Mainwaring RD, Murphy DJ, Rogers IS, Chan FP, Petrossian E, Palmon M, etal. Surgical repair of 115 patients with anomalous aortic origin of a coronary artery from a single institution. World J Pediatr Congenit Heart Surg. 2016;7(3):353– 9.

36. Mainwaring RD, Reddy VM, Reinhartz O, Petrossian E, Punn R, Hanley FL. Surgical repair of anomalous aortic origin of a coronary artery. Eur J Cardiothorac Surg. 2014;46(1):20– 6.

37. Mainwaring RD, Reddy VM, Reinhartz O, Petrossian E, MacDonald M, Nasirov T, etal. Anomalous aortic origin of a coronary artery:medium- term results aer surgical repair in 50 patients. Ann orac Surg. 2011;92(2):691– 7.

38. Feins EN, DeFaria Yeh D, Bhatt AB, Stefanescu A, Youniss MA, Ghoshhajra BB, etal. Anomalous aortic origin of a coronary artery:surgical repair with anatomic- and function- based follow- up. Ann orac Surg. 2016;101(1):169– 75; discussion 175– 66.

39. Turner II, Turek JW, Jaggers J, Herlong JR, Lawson DS, Lodge AJ. Anomalous aortic origin of a coronary artery:preoperative diagnosis and surgical planning. World J Pediatr Congenit Heart Surg. 2011;2(3):340– 5.

40. Herrmann JL, Goldberg LA, Khan AM, Partington SL, Brothers JA, Mascio CE, etal. A comparison of perioperative management of anomalous aortic origin of a coronary artery between an adult and pediatric cardiac center. World J Pediatr Congenit Heart Surg. 2016;7(6):721– 6.

41. Mitchell JH, Haskell WL, Raven PB. Classication of sports. J Am Coll Cardiol. 1994;24(4):864– 6.

42. Ong CS, Cameron DE, Jacobs ML. Surgical management of anomalous coronary arteries. Ann Cardiothorac Surg. 2018;7(5): 604– 10.

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Non- invasive investigation ofcoronary arterydisease

peak systole should return to 70– 80% of its baseline length with a

5.1 Echocardiography and stress echocardiography for coronary artery disease

Jae K. Oh

normal relaxation during the first third of diastole, but ischaemic myocardium has delayed myocardial relaxation. Diastolic strain imaging can identify this diastolic stunning phenomenon in patients with myocardial ischaemia many hours after cessation of chest pain.

Diagnosis ofcoronary arterydisease

Coronary artery disease (CAD) produces myocardial ischaemia and infarction which result in regional wall motion abnormalities. From multiple transducer positions, the entire left and right ventricular wall motion or contractility can be assessed visually and objectively using strain imaging. Based on the contractility of 16 segments of the left ventricle (LV), the wall motion score index (WMSI) is calculated using the following scoring system:0=normal motion, 1=mild hypokinesis, 2=moderate hypokinesis, and 3=severe hypokinesis to akinesis. The WMSI is an average value of summed wall motion scores. It has been shown to correlate well with the degree of perfusion defect, and to be prognostic after myocardial infarction. However, wall motion abnormalities can be present in patients without CAD as in stress cardiomyopathy. Moreover, wall motion abnormalities may not be present in patients with CAD, especially at a resting state. There is increasing evidence that systolic and diastolic strain imaging is more sensitive in detecting myocardial ischaemia or coronary disease than is wall motion (Fig. 5.1.1). Strain imaging measures the extent of myocardial deformation. It has been shown that systolic strain decreases in the area of severe coronary artery stenosis in the absence of a wall motion abnormality. Another interesting observation is the concept of diastolic stunning in myocardial ischaemia., Diastolic dysfunction occurs during an early stage of ischaemia and can last for several hours after cessation of ischaemia. Normally, shortened myocardium at

Fig.5.1.1 Strain imaging and stress echocardiography. Upper panel

shows systolic strain imaging (left) and diastolic strain imaging (right) with areas (arrow) of decreased thickening and relaxation, respectively, in two separate patients who had normal wall motion and were found to have circumﬂex and left anterior descending coronary artery stenosis, respectively. Bottom panel shows positive exercise (left) and dobutamine (right) stress echocardiography end- systolic images with administration of a contrast agent. Post- exercise images showed LV cavity dilatation and akinetic apex. With dobutamine, the LV became hyperdynamic and smaller until 30 mcg/ kg/ min dose, then it became larger with hypokinetic apex at peak dose.

SECTION 1 Pathophysiology and investigation ofcoronary artery disease40

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Stressechocardiography

Stress echocardiography compares digitally obtained real- time regional wall motion images before and aer induction of stress side by side. In patients with signicant CAD, but without myocardial infarction, resting wall motion is usually normal and becomes abnormal only with increased demand induced by a stress. Stress can be applied in the form of exercise or a pharmacological agent. Exercise can be performed using a supine bike which allows imaging at peak exercise or a treadmill which requires imaging of all LV segments

there is signicant viability, an akinetic segment contracts with a low dose of dobutamine, and then myocardial contractility becomes reduced at a higher dose aer initial improvement if there is signicant stenosis. is ‘biphasic’ response to dobutamine is the most specic nding for myocardial viability. e overall sensitivity and specicity of exercise echocardiography are similar to those of exercise thallium. e sensitivities of exercise echocardiography and exercise thallium for CAD in patients with single- , double- , or triple- vessel involvement were also similar (58%, 86%, and 94% versus 61%, 86%, and 94%, respectively).

within 90 seconds of termination of exercise. Dobutamine (from 5 to 40 mcg/ kg/ min) is the most commonly used pharmacological stress agent; it is oen used together with atropine if the target heart rate is not achieved at its maximum dose. It is oen necessary to admin-

Detection ofcomplications ofacute myocardialinfarction

ister a contrast agent (in about 50% of studies) to better delineate the LV endocardial borders for better wall motion visualization (Fig.

5.1.1). Complications from stress echocardiography are uncommon

(0.7% require treatment for arrhythmia), but well- trained medical personnel need to be present for monitoring nonetheless.

e normal response to exercise is an increase in myocardial contractility along with an increase in LV ejection fraction and a decrease in LV size. With myocardial ischaemia, the aected myocardial segment(s) becomes hypokinetic or even akinetic to dyskinetic. When myocardial ischaemia is severe, the LV becomes dilated with a reduction in the ejection fraction. However, reduction of LV ejection fraction and cavity dilatation are less common with dobutamine even when there is severe ischaemia. When exercise is used, peak or post- exercise wall motions are compared with those at rest. When dobutamine is used, wall motion at incremental dosage needs to be compared to that at a previously lower dose since wall motion may rst improve at a low dose, but decrease again at a higher dose (Fig.

5.1.1). is concept is used for identifying myocardial viability. If

Although the incidence of haemodynamic or structural complications from acute myocardial infarction has been reduced due to prompt revascularization by timely revascularization, they still occur and result in signicant morbidity and mortality. Echocardiography is the single most helpful diagnostic tool in this situation at the patient’s bedside using transthoracic, or frequently transoesophageal, echocardiography, which can facilitate appropriate medical and/ or surgical management to reverse the patient’s unstable situation. ese complications include severe LV systolic dysfunction, right ventricular infarction, coagulum tamponade due to free wall rupture, ventricular septal rupture, papillary muscle rupture (Fig. 5.1.2), dynamic LV outow tract obstruction with systolic anterior motion of the mitral valve, severe mitral regurgitation, intracardiac thrombus, and even right- to- le shunt in the setting of a right ventricular infarct. Diastolic function evaluation is also important in patients with myocardial infarction since it estimates LV lling pressure and predicts the long- term outcome. When a

Fig.5.1.2 Transoesophageal echocardiography of infarct complications. Transoesophageal echocardiography from two unstable patients after acute

myocardial infarction shows ruptured papillary muscle (arrow on the left) and ventricular septum (arrow on the right). Based on these images, they were taken to surgery.

5.2 Nuclearcardiology 41

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patient requires surgical treatment, transoesophageal echocardiography is performed intraoperatively to conrm the diagnosis and to assess the surgical result.

Echocardiography duringcoronary bypasssurgery

In many centres, intraoperative transoesophageal echocardiography is a routine part of anaesthetic management during coronary artery bypass gra (CABG) surgery. In on- pump CABG, transoesophageal echocardiography provides clear documentation of le and right ventricular function prior to initiation of cardiopulmonary bypass and again aer weaning from cardiopulmonary bypass when surgical revascularization is complete. e presence of new regional wall motion abnormality(ies) is an important indicator of incomplete revascularization, failed gra(s), or inadequate myocardial protection during cardioplegic arrest. In o- pump CABG, transoesophageal echocardiography provides vital early warning of new or worsening myocardial ischaemia and dysfunction, by monitoring right and le ventricular function in real time at intervals throughout the procedure. Worsening of ischaemic mitral regurgitation may be the rst sign of impending haemodynamic collapse and detection of worsening ischaemic mitral regurgitation during o- pump CABG surgery should prompt immediate modication of surgical technique or strategy.

Echocardiography forclinical trials incoronary arterydisease

Echocardiography is frequently utilized to provide inclusion parameters or as a secondary outcome such as ejection fraction, LV volumes, or the severity of mitral regurgitation. e STICH trial, which

2. Oh JK, Gibbons RJ, Christian TF, Gersh BJ, Click RL, Sitthisook S, etal. Correlation of regional wall motion abnormalities detected by two- dimensional echocardiography with perfusion defect determined by technetium 99m sestamibi imaging in patients treated with reperfusion therapy during acute myocardial infarction. Am Heart J. 1996;131(1):32– 7.

3. Choi JO, Cho SW, Song YB, Cho SJ, Song BG, Lee SC, etal. Longitudinal 2D strain at rest predicts the presence of le main and three vessel coronary artery disease in patients without regional wall motion abnormality. Eur J Echocardiogr. 2009;10(5):695– 701.

4. Sasaki S, Ito S, Kane G, Bois J, Anavekar N, Olson K, etal. Twodimensional diastolic speckle tracking echocardiography in the triage of patients with acute chest pain at emergency department. Eur Heart J. 2015;36:711– 4.

5. Ishii K, Imai M, Suyama T, Maenaka M, Nagai T, Kawanami M, etal. Exercise- induced post- ischemic le ventricular delayed relaxation or diastolic stunning:is it a reliable marker in detecting coronary artery disease? J Am Coll Cardiol. 2009;53(8):698– 705.

6. Tweet MS, Arruda- Olson AM, Anavekar NS, Pellikka PA. Stress echocardiography:what is new and how does it compare with myocardial perfusion imaging and other modalities? Curr Cardiol Rep. 2015;17(6):43.

7. Oh JK, Ding ZP, Gersh BJ, Bailey KR, Tajik AJ. Restrictive le ventricular diastolic lling identies patients with heart failure aer acute myocardial infarction. J Am Soc Echocardiogr. 1992;5(5):497– 503.

8. Khera S, Panza JA. Surgical revascularization for ischemic cardiomyopathy in the post- STICH era. Cardiol Rev. 2015;23(4):153– 60.

9. Kukulski T, She L, Racine N, Gradinac S, Panza JA, Velazquez EJ, etal. Implication of right ventricular dysfunction on long- term outcome in patients with ischemic cardiomyopathy undergoing coronary artery bypass graing with or without surgical ventricular reconstruction. J orac Cardiovasc Surg. 2015;149(5):1312– 21.

10. Deja MA, Grayburn PA, Sun B, Rao V, She L, Krejca M, etal.

Inuence of mitral regurgitation repair on survival in the surgical treatment for ischemic heart failure trial. Circulation. 2012;125(21):2639– 48.

compared medical therapy alone with CABG in patients with ischaemic cardiomyopathy, is a good example where echocardiography along with other imaging modalities was used to evaluate the treatment outcome. e following observations were made using imaging and clinical data from the STICH trial– :(1) CABG which provided a better 10- year survival compared to medical treatment alone was of more benet in patients with lower ejection fraction and/ or larger LV volume; (2)the presence of viability was not associated with better survival with CABG; (3)mitral valve surgery at

5.2 Nuclearcardiology

Aju P. Pazhenkottil and Ronny R. Buechel

the time of CABG appeared to provide incremental benet to the patients with moderate to severe mitral regurgitation; and (4)right ventricular dysfunction was a reection of worse LV status with lower LV ejection fraction, more mitral regurgitation, and higher LV lling pressure.

Technicalaspects

Principles ofsingle- photon emission computed tomography and positron emissiontomography

Single- photon emission computed tomography (SPECT) imaging is

REFERENCES

1. Lang RM, Badano LP, Mor- Avi V, Alalo J, Armstrong A, Ernande L, etal. Recommendations for cardiac chamber quantication by echocardiography in adults:an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28(1):1– 39.e14.

based on the principle of perfusion- dependent tracer uptake into myocytes. While the radiotracer decays, the subsequently emitted photons are registered by the detectors made of very high- density inorganic crystals. As with SPECT, the basic principle of positron emission tomography (PET) is based on the detection of photons originating from radionuclide decay. Contrary to SPECT, which relies on radiotracers with gamma decay, PET radionuclides exhibit positive beta decay with a much shorter half- life which mandates an

SECTION 1 Pathophysiology and investigation ofcoronary artery disease42

(a)

(c)

(e)

(b)

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on- site cyclotron for rapid production. Importantly and unlike any other modality, PET allows for absolute quantication of myocar-

electrocardiogram- triggering and within a single breath- hold— can

be used to additionally assess the coronary artery calcium score. dial blood ow (MBF) which improves accuracy for the detection of coronary artery disease (CAD) and renders this modality the noninvasive gold standard for assessing myocardial perfusion.

Attenuationcorrection

e majority of all photons emitted during the decay process are attenuated or deected along their path due to inhomogeneous density of dierent structures within the human body. Hence, the count rate at the detectors is reduced. In SPECT, the photon energies are relatively low (e.g. 140 keV with technetium- 99m (mTc)) and, thus, more susceptible to attenuation compared to PET (511 keV with positron- emitting radionuclides). Among various techniques, computed tomography (CT) has shown the most promising results for attenuation correction. While most current PET scanners are hybrid devices equipped with a CT system for attenuation correction by default, most current dedicated SPECT scanners do not oer an integrated CT. However, this can easily be overcome by using a standalone CT device to create low- dose, non- enhanced scans of the chest which are aerwards manually co- registered with the emission scans. Furthermore, those native CT scans— if acquired with

Single- photon emission computedtomography

Radiotracers

Current radiotracers for SPECT perfusion imaging include mTc-

sestamibi, mTc- tetrofosmin, and thallium- 201 (Tl). e use of

mTc- based tracers is recommended by current guidelines because

of their higher photon energy leading to higher count rates at the

detector and, hence, better image quality at a much lower radiation

exposure compared to Tl.

Camera designs and latestadvances

Since the introduction of the rst SPECT camera, changes in

camera designs were conned to optimizing the performance of de-

tectors and to implementing multiple detectors in a single system.

Furthermore, with the increasing demand for cardiac SPECT,

manufacturers have released a number of devices that are specif-

ically dedicated to cardiac imaging (Fig. 5.2.1). Arecent revolu-

tionary advancement in technical innovation for cardiac SPECT has

(d)

(f)

Fig.5.2.1 Avariety of dedicated cardiac SPECT cameras:(a) CardiArc

(d)Ventri™, GE Healthcare; (e)D- SPECT®, Spectrum Dynamics; (f)Discovery™ NM 530c, GE Healthcare.

, CardiArc Ltd; (b)CardioMD®, Philipps Healthcare; (c)Cardius® 3 XPO, Digirad;

5.2 Nuclearcardiology 43

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been the introduction of semiconductor detector technology using the cadmium– zinc– telluride (CZT) technique, which diers fundamentally from a conventional sodium iodide detector. It allows direct conversion of light into an electrical signal. us, contrary to conventional systems, CZT detectors avoid the need for bulky photomultiplier tubes, thereby reducing the size of the detector head and improving the theoretical in- plane resolution. Additionally, the intrinsic spatial resolution of current CZT detectors is substantially better than with conventional sodium iodide detectors (i.e. 4mm vs 10mm). us, instantaneous acquisition of cardiac activity from dierent projection angles becomes possible. e combination of this technology with modern iterative reconstruction algorithms in such novel dedicated cardiac camera systems has led to a ve- to tenfold increase in system sensitivity and twofold increase in image resolution. is allows imaging of the heart in less than 5 minutes, while at the same time yielding images with substantially better image quality at higher resolutions than do state- of- the- art conventional SPECT cameras. As an alternative to shortened acquisition time, this new technology can be used to reduce tracer activity and, consequently, eective radiation exposure.

Clinicalvalue

Perfusion abnormalities, induced through physical exercise or pharmacological stimulation using intravenous dobutamine or adenosine, are used to detect obstructive CAD. e functional information provided by SPECT myocardial perfusion imaging has been demonstrated to confer excellent diagnostic value in CAD detection. Furthermore, and unlike any other modality, SPECT possesses long- term follow- up information in tens of thousands of patients, which rmly establish the important role of this modality for risk stratication of CAD patients, for guiding patient management, and for optimization of downstream resource utilization.

being tested in phase III trials. Radionuclide tracers should ideally full several radiokinetic properties, such as high rst- pass extraction fraction and a linear correlation of tracer uptake with MBF rate. Moreover, prolonged retention in the heart to give a stable distribution and high count statistics is necessary so that electrocardiogramgating is possible for the simultaneous assessment of both perfusion and le ventricular function.

Detection ofischaemia

Compared to the more widely available SPECT technique, PET oers several advantages for the detection and characterization of CAD. PET scanners have higher spatial resolutions and count sensitivities than do SPECT scanners. Available PET studies with NNH or Rb report a high diagnostic performance with weighted sensitivity and specicity of 90% and 89%, respectively, which is approximately 3– 5% higher than it is for SPECT imaging. Hence, especially in patients aer coronary artery bypass graing, PET is generally regarded as the preferred imaging method to assess ischaemia. Available data documenting the predictive value of PET consistently demonstrated a graded inverse relationship between the extent of perfusion abnormalities on PET and cardiovascular outcomes.

The added value ofmyocardial blood ﬂowquantiﬁcation

One of the most distinct advantages of PET over other imaging modalities is the ability to provide regional absolute quantication of MBF. While there are not enough data to support an added diagnostic value of quantitative MBF measurements over perfusion imaging alone, the potential clinical utility of measuring MBF has been shown in prognostic studies demonstrating an independent prognostic value of myocardial perfusion abnormalities and coronary ow reserve assessed with N- NH PET over a follow- up of 5.4years. Of note, in patients with normal perfusion, abnormal

Positron emissiontomography

Radiotracers

ere are several radiolabelled compounds which are used in cardiac PET applications. e most common are summarized in Tab l e

5.2.1. Of them, N- ammonia, O- water, and Rb are clinically

used for myocardial perfusion imaging, while F- FDG is used to assess myocardial viability. Apromising radionuclide agent not yet in clinical use is F- urpiridaz, holding great potential and currently

coronary ow reserve was independently associated with a higher annual event rate over 3years compared with normal coronary ow reserve (6.3% vs 1.4%).

Assessment ofmyocardialviability

Dysfunctional but viable myocardium can exist in a state of hibernation (where glucose uptake is preserved or even increased but contractility impaired) and can recover its contractility upon adequate restoration of blood ow. FDG PET studies have a weighted sensitivity and specicity of 92% and 63%, respectively, to predict regional

Table5.2.1 Characteristics ofthe most common cardiac PET tracers

Physical half- life 2 min 10 min 78 sec 110 min

Labelled compound

Radionuclide production Cyclotron Cyclotron Generator Cyclotron

Uptake mechanism Free diffusion Metabolically trapped in

Indication Myocardial perfusion Myocardial perfusion Myocardial perfusion Glucose metabolism/ viability

Myocardial blood ﬂow quantiﬁcation

O- H2O

O- water

Excellent Good Moderate –

N- NH

N- ammonia

myocardium

Rubidium

Na/ K- ATPase Metabolically trapped in myocardium

F- FDG

F- ﬂuorodeoxyglucose

Glucose transport/ hexokinase

assessment

SECTION 1 Pathophysiology and investigation ofcoronary artery disease44

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Fig.5.2.2 Cardiac hybrid image of a patient after coronary artery bypass grafting. The right internal thoracic artery graft to the right coronary artery

appears unremarkable with normal perfusion of the inferior wall, while the venous graft to the ﬁrst diagonal branch and the left circumﬂex artery shows signiﬁcant stenosis (arrow) leading to a large ischaemic area of the anterolateral wall (arrowheads).

functional recovery, and 83% and 64%, respectively, to predict global recovery of le ventricular function aer revascularization. Nonetheless, only limited prospective data is available assessing the impact on prognosis of viability assessment by FDG PET. 

Hybridimaging

Rapid advances in coronary computed tomography angiography (CCTA) technology have facilitated hybrid PET/ CCTA and SPECT/ CCTA imaging allowing comprehensive assessment of anatomical and functional information simultaneously. Hybrid imaging is especially helpful in patients with multivessel disease, signicant side- branch disease, and chronic total occlusions. Moreover, it is most useful to exactly allocate an ischaemic myocardial region to its subtended coronary artery or bypass gra, respectively (Fig. 5.2.2), which allows development of appropriate treatment strategies and target vessel revascularization. Beside its superior diagnostic accuracy, recent studies have documented the prognostic value of cardiac hybrid imaging.,

Conclusion

Nuclear imaging has contributed signicantly to our increasing understanding of CAD and is now considered a cornerstone for the diagnosis and management of CAD. Compared to conventional stress electrocardiography, imaging- based diagnostic stress tests oer superior diagnostic accuracy and therefore recent guidelines endorse the use of imaging in chronic coronary syndromes patients whenever local availability and expertise allows.

REFERENCES

1. Gould KL. Does coronary ow trump coronary anatomy? JACC Cardiovasc Imaging. 2009;2(8):1009– 23.

2. Schepis T, Gaemperli O, Koepi P, Rüegg C, Burger C, Leschka S, etal. Use of coronary calcium score scans from stand- alone multislice computed tomography for attenuation correction of myocardial perfusion SPECT. Eur J Nucl Med Mol Imaging. 2007;34(1):11– 9.

3. Imbert L, Poussier S, Franken PR, Songy B, Verger A, Morel O, etal. Compared performance of high- sensitivity cameras dedicated to myocardial perfusion SPECT:a comprehensive analysis of phantom and human images. J Nucl Med. 2012;53(12):1897– 903.

4. Buechel RR, Herzog BA, Husmann L, Burger IA, Pazhenkottil AP, Treyer V, etal. Ultrafast nuclear myocardial perfusion imaging on a new gamma camera with semiconductor detector technique:rst clinical validation. Eur J Nucl Med Mol Imaging. 2010;37(4):773– 8.

5. de Jong MC, Genders TS, van Geuns RJ, Moelker A, Hunink MG. Diagnostic performance of stress myocardial perfusion imaging for coronary artery disease:a systematic review and metaanalysis. Eur Radiol. 2012;22(9):1881– 95.

6. Shaw LJ, Iskandrian AE. Prognostic value of gated myocardial perfusion SPECT. J Nucl Cardiol. 2004;11(2):171– 85.

7. Kim DY, Kim HS, Reder S, Zheng JH, Herz M, Higuchi T, etal. Comparison of 18F- labeled uoroalkylphosphonium cations with 13N- NH3 for PET myocardial perfusion imaging. J Nucl Med. 2015;56(10):1581– 6.

8. Parker MW, Iskandar A, Limone B, Perugini A, Kim H, Jones C, etal. Diagnostic accuracy of cardiac positron emission tomography versus single photon emission computed tomography for coronary artery disease:a bivariate metaanalysis. Circ Cardiovasc Imaging. 2012;5(6):700– 7.

9. Herzog BA, Husmann L, Valenta I, Gaemperli O, Siegrist PT, Tay FM, etal. Long- term prognostic value of 13N- ammonia myocardial perfusion positron emission tomography added value of coronary ow reserve. J Am Coll Cardiol. 2009;54(2):150– 6.

10. Camici PG, Prasad SK, Rimoldi OE. Stunning, hibernation, and assessment of myocardial viability. Circulation. 2008;117(1):103– 14.

11. Schinkel AF, Bax JJ, Poldermans D, Elhendy A, Ferrari R, Rahimtoola SH. Hibernating myocardium:diagnosis and patient outcomes. Curr Probl Cardiol. 2007;32(7):375– 410.

5.3 Magnetic resonanceimaging 45

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12. Beanlands RS, Nichol G, Huszti E, Humen D, Racine N, Freeman M, etal. F- 18- uorodeoxyglucose positron emission tomography imaging- assisted management of patients with severe le ventricular dysfunction and suspected coronary disease:a randomized, controlled trial (PARR- 2). J Am Coll Cardiol. 2007;50(20):2002– 12.

13. Gaemperli O, Kaufmann PA, Alkadhi H. Cardiac hybrid imaging. Eur J Nucl Med Mol Imaging. 2014;41(Suppl

1):S91– 103.

14. Pazhenkottil AP, Nkoulou RN, Ghadri JR, Herzog BA, Küest SM, Husmann L, etal. Impact of cardiac hybrid single- photon emission computed tomography/ computed tomography imaging on choice of treatment strategy in coronary artery disease. Eur Heart J. 2011;32(22):2824– 9.

15. Pazhenkottil AP, Nkoulou RN, Ghadri JR, Herzog BA, Buechel RR, Küest SM, etal. Prognostic value of cardiac hybrid imaging integrating single- photon emission computed tomography with coronary computed tomography angiography. Eur Heart J. 2011;32(12):1465– 71.

16. Pazhenkottil AP, Benz DC, Gräni C, Madsen MA, Mikulicic F, von Felten E, etal. Hybrid SPECT perfusion imaging and coronary CT angiography:long- term prognostic value for cardiovascular outcomes. Radiology. 2018;288(3):694– 702.

17. Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, FunckBrentano C, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2019 (00 ):1– 71

5.3 Magnetic resonanceimaging

Alexander Gotschy and Robert Manka

Introduction

Cardiovascular magnetic resonance (CMR) is a multifunctional imaging modality that allows the assessment of various parameters of cardiovascular function and morphology such as ejection fraction, coronary artery status, myocardial perfusion and viability, tissue characterization, vascular ow, and others. e most important tasks for non- invasive imaging in coronary artery disease (CAD) are the identication of ischaemia and the detection of viability in ischaemic regions to decide which myocardial segments will prot from revascularization. Due to technical developments such as parallel imaging, k- t- undersampling strategies, or compressed sensing, the examination times to obtain such information with CMR may be reduced to less than 40 minutes. Compared with nuclear imaging modalities for the assessment of myocardial perfusion, CMR has the advantage of no exposure to ionizing radiation for the patient. ACMR examination for perfusion and viability is usually embedded in a CMR protocol that contains at least cine sequences for the assessment of cardiac function and volumes (Fig. 5.3.1). Other imaging modules can be added as required.

(a)(b) (c)

(d) (e)(f)

Fig.5.3.1 Exemplary still frames of cine sequences (steady- state free precession or spoiled gradient echo) in the three long- axis views— two-

chamber view (a), three- chamber view (b), and four- chamber view (c)— and short- axis orientation— basal (d), mid- ventricular (e), and apical (f)— for the assessment of left ventricular and right ventricular geometry, global function, wall motion abnormalities, pericardial effusion, and qualitative evaluation of the valves.

SECTION 1 Pathophysiology and investigation ofcoronary artery disease46

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Imaging ofmyocardialischaemia

For the detection of ischaemia, CMR provides two techniques that are relevant for clinical practice. First, CMR perfusion imaging during vasodilator (adenosine or regadenoson)- induced hyperaemia, and second, dobutamine stress CMR (DSMR) to reveal stress- induced wall motion abnormalities caused by ischaemia. Both methods have proven excellent prognostic value in patients with known or suspected CAD.–  CMR perfusion imaging visualizes the passage of a gadolinium- based contrast agent (CA) through the myocardium under hyperaemic conditions. Since coronary arteries with relevant stenoses cannot adequately respond to the vasodilator, CA inux is delayed leading to a dark delineation of ischaemic territories (Fig. 5.3.2a). e rst- pass of the CA lasts about 10 seconds, therefore the CMR sequence is performed during a breath- hold to eliminate respiratory motion artifacts. Aer the vasodilator stress, a CMR perfusion image at rest may be obtained to rule out false- positive results due to imaging artifacts (Fig. 5.3.2b). Usually, three axial slices are acquired, to assess perfusion decits in the basal, mid- ventricular, and apical segments of the myocardium. Novel three- dimensional CMR perfusion techniques allow for the assessment of the myocardial ischaemic burden as percentage of the myocardium at risk and have proven to be highly accurate and reproducible in the evaluation of CAD. CMR perfusion imaging can be performed at 1.5 telsa (T)and 3 T; however, most clinical

evidence is based on data obtained at 1.5 T.In addition, CMR allows the direct evaluation of the coronary arteries using magnetic resonance coronary angiography. In a clinical trial, adding a magnetic resonance coronary angiography examination to a standard CMR perfusion protocol led to enhanced diagnostic accuracy. In experimental studies, combining three- dimensional CMR perfusion with a magnetic resonance coronary angiography examination allowed the generation of hybrid images depicting the coronary tree with the underlying myocardial perfusion, demonstrating the potential to unambiguously correlate coronary stenoses with non- distinct perfusion decits. Large multicentre trials have demonstrated the superiority of CMR perfusion imaging compared to single- photon emission computed tomography perfusion imaging, showing a signicantly higher sensitivity and better performance in particular in patients with multivessel disease.–  Adenosine- based vasodilator stress is contraindicated in patients with high- grade atrioventricular block, sinus node dysfunction, and severe obstructive lung disease/ asthma as well as signicant hypo- or hypertension or acute heart failure.

As an alternative to CMR perfusion imaging, DSMR can be performed to investigate myocardial ischaemia. ADSMR examination is similar to stress echocardiography. Under the pharmacological stress of increasing doses of dobutamine, ischaemic regions are identied by monitoring regional le ventricular wall motion in four standard cine- CMR sequences (two- chamber, three- chamber,

(b)

(a)

(c)

(d)

(e)

Fig.5.3.2 This 62- year- old patient with known CAD and a history of myocardial infarction in the left circumﬂex artery territory 6years ago was

referred for CMR with clinical suspicion of progression of the CAD. CMR perfusion revealed a vasodilator- induced hypoperfusion ((a) left to right:basal, mid- ventricular, apical) in the anterior and anterioseptal segments that was not present at rest (b). LGE imaging (c)showed preserved viability in the ischaemic regions but a myocardial scar in the lateral segments corresponding to the prior myocardial infarction. The ischaemic regions correlated with a subtotal occlusion of the left anterior descending artery in the coronary angiography (d)while the right coronary artery shown only non- signiﬁcant wall irregularities (e).

Transmurality of scar

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5.3 Magnetic resonanceimaging 47

0–25%

(a)(b) (c) (d)

60–79% 42%10%

26–50% 51–75% 76–100%

Likelihood of increased contractility after revascularization

Fig.5.3.3 In ischaemic segments, the potential for functional recovery depends on the transmural extend of scar. This ﬁgure shows LGE images of

four different patients with increasing transmurality of scar from left to right:(a) no scar, (b)subendocardial lateral scar of 25– 50% transmurality, (c)large septal and anterior scar with 50– 75% transmurality, (d)extensive transmural scar in the anteroseptal, anterior, and inferior segments. The lower row depicts the likelihood of increased contractility after revascularization corresponding to the different stages of transmurality.

Kim RJ, Wu E, Rafael A, Chen EL, Parker MA, Simonetti O, etal. The use of contrast- enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med. 2000;343(20):1445– 53.

four- chamber, and short- axis view). Compared with stress echocardiography, DSMR has shown a signicantly higher diagnostic accuracy. In a direct comparison with vasodilator CMR perfusion imaging, DSMR showed similar performance for the assessment of CAD. e complication rate of DSMR is comparable to those of other imaging modalities using dobutamine/ atropine stress and consists mostly of acute rhythm disorders. In rare cases, sustained (event rate 0.1%) or non- sustained (0.4%) ventricular tachycardia or atrial brillation (1.6%) may occur, making the availability of experienced personnel, continuous rhythm monitoring, and the debrillation equipment/ advanced cardiac life support imperative. Contraindications for the administration of dobutamine are acute coronary syndromes, severe aortic stenosis, severe hypertension, hypertrophic obstructive cardiomyopathy, acute peri- / endocarditis, and glaucoma.

Imaging ofmyocardialviability

e investigation of myocardial viability is important to discriminate dysfunctional, ischaemic myocardium that has the potential to recover aer revascularization from non- viable necrotic or scar tissue. Both states may appear as hypoperfused regions in CMR perfusion imaging or regions with impaired wall motion in DSMR, respectively. Myocardial stunning as well as hibernation can impair wall motion in viable myocardium. Using CMR, the late gadolinium enhancement (LGE) method is a sensitive technique to dierentiate viable myocardial tissue from irreversibly damaged myocardium and scar tissue. e LGE technique uses gadolinium- based CAs that can only disperse in the extracellular space. About 10– 20 minutes aer administration, the distribution of the CA reaches an equilibrium. e infarcted myocardium and scar tissue has a higher percentage of extracellular space compared

to viable myocardium so that gadolinium accumulates in those scarred tissues. erefore, necrotic myocardium and scare tissue are delineated as areas of hyperenhancement in T- weighted LGE images. For imaging LGE, T- weighted inversion recovery gradient echo sequences are used (Fig. 5.3.2c). Typically, those sequences are run in the standard two- chamber, three- chamber, and fourchamber views with an additional stack of short- axis views. With a high spatial resolution that ranges from 1.5 × 1.5mm² to the submillimetre level, CMR- based LGE imaging allows for the detection of microinfarcts and infarcts with incomplete transmurality. e transmurality of a necrotic or scar region correlates inversely with the potential to recover aer revascularization (Fig. 5.3.3). High rates of functional recovery can be observed in ischaemic segments with less than 50% transmural scar (Fig. 5.3.3a,b), while segments with a larger transmurality of LGE exhibit a low likelihood of increased contractility aer revascularization (Fig.

5.3.3c,d). Positron emission tomography and single- photon emis-

sion computed tomography are also established methods for the assessment of myocardial viability and scar tissue aer myocardial infarction. However, compared with those nuclear imaging techniques, CMR provides a higher spatial resolution, leading to a better diagnostic accuracy for the detection of subendocardial scar tissue.

REFERENCES

1. Jahnke C, Nagel E, Gebker R, Kokocinski T, Kelle S, Manka R, etal. Prognostic value of cardiac magnetic resonance stress tests:adenosine stress perfusion and dobutamine stress wall motion imaging. Circulation. 2007;115(13):1769– 76.

2. Lipinski MJ, McVey CM, Berger JS, Kramer CM, Salerno M. Prognostic value of stress cardiac magnetic resonance imaging in patients

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