Pediatric and Congenital Cardiology, Cardiac Surgery and Intensive Care 9781447149996

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Emerging Role of Stress Perfusion Cardiovascular Magnetic Resonance in the Patient with Congenital Heart Disease Andrew M. Crean, Djeven P. Deva, and Rachel Wald

Contents

Interpretation of Stress Perfusion CMR . . . . . . . . . . . 10

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Limitations of Stress Perfusion CMR . . . . . . . . . . . . . . 11

Limitations of Conventional Methods of Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Treadmill Stress CMR: Perfusion and Wall Motion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

The Comprehensive Nature of the CMR Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Data from the Adult Ischemic Stress CMR World . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Limitations of CMR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Physical Preparation of the Stress Patient . . . . . . . . .

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Mental Preparation of the Stress Patient . . . . . . . . . .

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Choice of Vasodilator Agent . . . . . . . . . . . . . . . . . . . . . . . .

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Assessment of Vasodilator Effect on the Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Monitoring for Stress Perfusion CMR . . . . . . . . . . . . .

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Practical Aspects of Performing Stress Perfusion CMR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Stress Perfusion CMR in Patients Following Arterial Switch . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Stress Perfusion CMR for Anomalous Left/Right Coronary Artery from the Pulmonary Artery (ALCAPA/ARCAPA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Stress Perfusion CMR in Kawasaki Disease . . . . . . . 14 Stress Perfusion CMR in Assorted Other Congenital Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

A.M. Crean (*) Division of Cardiology, University of Cincinnati Medical Center and Cincinnati Children’s Hospital Medical Center and Joint Department of Medical Imaging, Toronto General Hospital, Toronto, Canada e-mail: [email protected] D.P. Deva Department of Medical Imaging, St Michael’s Hospital, Toronto, Canada e-mail: [email protected] R. Wald Division of Cardiology and the Joint Department of Medical Imaging, Toronto General Hospital, Toronto, Canada e-mail: [email protected] # Springer-Verlag London 2016 E.M. Da Cruz et al. (eds.), Pediatric and Congenital Cardiology, Cardiac Surgery and Intensive Care, DOI 10.1007/978-1-4471-4999-6_250-1

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Abstract

Rapid advances in surgical repair of congenital heart disease has led to ever increasing numbers surviving into adult life. A proportion of adult congenital heart disease (ACHD) patients will have had direct surgical intervention upon the coronary arteries which renders them vulnerable to issues in later life. There is no accepted method for either the surveillance of these patients nor for their investigation when presenting with new symptoms. This chapter argues for a shift in paradigm away from testing associated with radiation (nuclear techniques, computed tomography, coronary angiography) to a paradigm where stress perfusion cardiac magnetic resonance (CMR) imaging is used as a gatekeeper to determine who needs go on for formal catheterization. The technique of stress perfusion CMR is discussed along with its benefits and weaknesses. Practical illustrations of the technique’s utility are provided throughout the chapter. Keywords

Anomalous left/right coronary artery from the pulmonary artery (ALCAPA/ARCAPA) • Arterial switch • Calcified conduits and calcific masses • Cardiovascular magnetic resonance (CMR) • Congenital heart disease (CHD) • Coronary surveillance • Dark-rim artifact (DRA) • Dipyridamole • Ischemic stress CMR • Kawasaki disease • Nitinol-based devices • Perfusion imaging • Regadenoson • Stress perfusion CMR • Treadmill stress • Vasodilator

Introduction The success story that has been the surgical management of patients with congenital heart disease (CHD) over the last 50 years has brought its share of challenges due to the “unnatural history” following repair. Our patients are not only born with coronary anomalies but may have coronary abnormalities created by the surgical procedures themselves. Although we tend to think of the rare and

fascinating coronary anomalies – the anomalous left or right coronary artery from the pulmonary artery, the anomalous left or right coronary artery from the opposite sinus, etc. – these patients are in fact outnumbered by those who have undergone coronary reimplantation procedures as part of a Ross, Bentall, or Jatene arterial switch operation. This latter group represents a particularly interesting challenge for management and surveillance for several reasons: this is not a rare operation at any large congenital center; the patients need to be followed for many years; as children the typical presentations of ischemic chest pain recognized in the adult may be absent; and sudden cardiac death has been occasionally reported as an unfortunate first (and last) indicator of a previously unsuspected coronary problem. There is a second large group of patients who are typically also followed by pediatric cardiologists (and then often graduate to adult congenital cardiologists), despite being born with structurally normal hearts – these are the children who succumb to Kawasaki disease, a proportion of whom will develop cardiac abnormalities as part of the inadequately named mucocutaneous lymph node syndrome. The coronary aneurysms that result in some cases may have important effects on distal coronary flow that pass unrecognized, particularly in children, and the natural history of these aneurysms in adult life is not well understood. Regular coronary surveillance is therefore appropriate for several patient populations followed in congenital heart centers. The literature supplies advocates for almost any of the available imaging modalities: computed tomography, echo, nuclear, and catheterization, although there are almost no large studies in this area. In this chapter, we would like to present our experience that stress perfusion cardiovascular magnetic resonance (CMR) imaging is not only the most appropriate test for these children and young adults but is also – quite simply – the most complete of the imaging modalities. The following section will discuss in greater detail the comprehensive nature of CMR, while subsequent sections will deal with the practical procedural elements of performing stress CMR, its applications in the patient groups

Emerging Role of Stress Perfusion Cardiovascular Magnetic Resonance in the Patient with. . .

described, the evidence base for stress CMR in the adult ischemic world, and the (very) limited current data on stress CMR for patients with congenital heart disease.

Limitations of Conventional Methods of Assessment One of the unique challenges facing congenital heart patients is the requirement for lifelong follow-up. In patients with coronary “issues” or in whom coronary artery reimplantation has been performed, this challenge is particularly relevant. As physicians we seek to limit radiation exposure to our patients, and yet many of our conventional methods for assessing the coronary arteries involve ionizing radiation. The use of ionizing radiation in congenital populations was described in a recent European-wide registry, which highlighted the potential for significant cumulative lifetime doses in our patients [17]. There has historically been a very heavy dependence upon cardiac catheterization in congenital heart disease. Not only is it available at every major center, it provides unparalleled visualization of the coronary arteries with a spatial resolution that is still not really approached by a modern method of noninvasive imaging. While this is certainly necessary in the preoperative period or if there are major coronary concerns, catheterization is expensive, is disliked by some patients, and comes with a small risk of serious morbidity and death. It is thus not an ideal technique to use in routine follow-up for coronary surveillance, although even in this situation it has its advocates. Perfusion imaging with radionucleotide isotopes (thallium, technetium, etc.) has been available for many years, is easy to perform and readily available, and is well tolerated by patients. The basis of perfusion imaging (nuclear and magnetic resonance) is the induction of differential tracer flow down the arteries which vasodilate normally versus those which are narrowed, distorted, or obstructed. Stress may be performed by treadmill exercise in which case there is also the advantage of having workload data and assessment of ECG

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change. For congenital patients who are unable to exercise adequately, vasodilators such as adenosine or dipyridamole may be used to induce coronary hyperemia (note not ischemia – a common misconception regarding vasodilator stress). Vasodilator stress is well tolerated and incredibly safe with a very low major adverse cardiac event rate borne out by millions of pharmacologic stress nuclear studies throughout the world. For reasons of availability, ease of performance, and patient acceptability, nuclear stress perfusion has become widely accepted as one of several “firstchoice” techniques in European and (particularly) North American congenital institutions. However, physicians referring their patients for these studies often have only a hazy idea at best of the dose associated with this test [5]. Many are surprised to learn that it is equivalent in dose to roughly 3–4 coronary angiograms (technetium – rest/stress dose approximately 15 mSv) or as high as 8 coronary angiograms (thallium – rest/stress dose approximately 40 mSv). While all data linking exposure to subsequent cancer is questionably based upon theoretical assumptions derived from the Nagasaki and Hiroshima events – as well as an unproven assumption of a linear no-threshold relationship between dose and malignancy – physicians are nevertheless appropriately seeking to shield their (young, radiosensitive) patients from the excesses of the past. A further limitation of nuclear cardiology reflects the physical limitation of current equipment. Post-collimator spatial resolution is in the order of 8–10 mm – since this is approximately the same as transmural myocardial thickness, it can be difficult to recognize subendocardial ischemia or balanced three-vessel disease. This is a point we will return to in subsequent discussion about stress perfusion cardiovascular magnetic resonance (CMR) imaging. Treadmill stress echo has been historically underused in congenital populations for reasons that are not entirely clear but may reflect dominant adult experience in the ischemic world with much lower levels of experience/confidence in the technique in pediatric institutions. However, even adult congenital institutions appear less enthused with this method of assessment compared to the

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alternatives of single-photon computed emission tomography (SPECT) or CMR imaging. This is a pity because the need in coronary surveillance is to rule out significant flow limitation – which is something stress echo does particularly well. A further advantage is the availability, again, of workload and ECG data. Finally, of course, there is no exposure to ionizing radiation at all with this technique, making it attractive for long-term follow-up. Patients unable to adequately raise their heart rate by exercise can be stressed by dobutamine infusion with little or no change in the sensitivity and specificity of the test. One limitation of the technique is the need for a reasonable echo window, which may be difficult or limited in patients with chest wall deformity or simple obesity. There is also a rather unquantifiable “impression” among many cardiologists that reading stress echo is a rather dark art and somewhat subjective. While these authors would challenge that opinion, there is of course little or no data to support the argument either way in the congenital field. It is fair to say that the whole area of imaging in congenital heart disease is riddled with opinions, conjecture, and personal beliefs stated as gospel truth. Data are very limited even for wellestablished techniques like SPECT, are almost nonexistent for stress echo, and are only just starting to emerge for stress CMR. In the rest of this chapter, the authors will share their bias in favor of stress CMR, explaining why we hold these opinions and what little published evidence exists.

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demonstrated by administering gadoliniumbased contrast agents (magnetic resonance angiography) and myocardial scarring identified using the technique of late gadolinium enhancement (LGE) imaging in which images of the heart are acquired 10–15 min after a bolus of contrast, allowing for differential washout between normal and abnormal areas of the myocardium [8]. Through a process of cardiac gating to the ECG, it is possible to acquire so-called “segmented” cine images in which data acquired over a number of heart beats is used to build up a composite beating image of the heart with an effective temporal resolution in the order of 35 milliseconds. Similar techniques can be employed to visualize flow in vascular structures providing information (via a very different physical principle) similar to Doppler echocardiography [28]. Phase-contrast imaging of this sort allows for the relatively precise measurement of flow volumes as well as peak and mean velocity in the user-defined region of interest. Finally, userdefined imaging planes can be prescribed in any orientation to acquire anatomically helpful images aligned to the anatomy of interest without any limitation by body shape or imaging “window.” Therefore – in a comprehensive CMR exam – it is possible to acquire valuable information about anatomy, function, flow, perfusion, and fibrosis in a protocol that takes less than 60 min to perform and without any ionizing radiation at all.

Limitations of CMR Despite its many advantages, CMR has several

The Comprehensive Nature of the CMR important limitations. The magnet bore is claustrophobic to a small percentage of individuals Examination The principal advantage of CMR over all other forms of imaging is its comprehensive nature. Manipulation of the water protons intrinsic to the patient by use of strong switching magnetic fields results in the ability to characterize tissue with much greater contrast resolution than any other technique. Various “weightings” can be applied, designed to enhance the visibility of edema, fibrosis, thrombus, etc. Vascular structures can be

with an examination refusal or non-completion rate of around 5 %. The newer magnets with a 70 cm diameter bore compare favorably with the standard 60 cm bore present in most 1.5 T systems, although the latter remain much more prevalent. Some patients who appear initially reluctant to enter the magnet can be reassured by a combination of either medication or eye shield. Pediatric institutions sometimes have third-party equipment that makes it possible to show videos inside

Emerging Role of Stress Perfusion Cardiovascular Magnetic Resonance in the Patient with. . .

the magnet (using specially adapted goggles), which greatly improves scanning tolerance in children older than 5 years. Implanted medical devices fall into two categories – those such as pacemakers, defibrillators, and aneurysm clips are considered relatively solid contraindications to routine CMR, although there is a growing literature surrounding safe scanning of patients with the first two types of device. The second category relates to implanted ferromagnetic devices which pose no safety issue to a patient in a scanner but may significantly impair local image quality due to disturbance of magnetic field uniformity. Such devices include BlalockTaussig shunt clips, atrial septal defect closure devices, metallic heart valves, coronary stents, Harrington spinal rods, etc. However, the greatest degree of field distortion is seen with stainless steel coils used for vessel embolization, as well as Fontan fenestration closure devices – the level of artifact from these often precludes adequate visualization of the anatomy in question. Nitinolbased devices, in contrast, cause relatively focal field disturbance such that patients who have had nitinol atrial septal defect closure devices can usually be scanned without problem. On further peculiarity of CMR is its relatively poor sensitivity for identifying calcium. This is because the protons within calcified structure are fixed in a relatively rigid lattice and do not generate much signal. Calcified conduits and calcific masses may therefore occasionally be overlooked by CMR since they tend to simply appear dark – with experience, this appearance is usually recognizable. Finally, the magnet is not an ideal environment for sick patients. Not only do unwell patients rarely tolerate the breath-hold and prolonged examination times that may be required, but hemodynamically unstable patients cannot be managed safely due to limitations of access and monitoring. Similarly patients with cognitive impairment often find it impossible to lie still and follow commands regularly, leading to blurred and suboptimal studies. In all of these situations, the most acceptable solution is often to consider an alternative test or else to proceed with full general anesthesia, proper monitoring,

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and trained support. Magnet-compatible anesthesia machines and crash trolleys are available but attention also needs to be paid to the proper screening of itinerant anesthesiology personnel to ensure magnet safety. Contraindications to stress CMR are relatively few and reflect the usual contraindications to any MR exam (non-MR-compatible devices, claustrophobia, pregnancy, etc.) as well as the standard contraindications to vasodilator stress agents (asthma, regular dipyridamole use, second- or third-degree heart block).

Physical Preparation of the Stress Patient The commonest reason for an inadequate stress examination is consumption of caffeine in the 24 h preceding the test. Caffeine acts as a competitive antagonist at the adenosine receptor and may lead to an inadequate vasoactive response with submaximal coronary hyperemia. Since it is hard to recognize whether maximal hyperemia has been reached clinically, it is common practice among stress labs to ban caffeine consumption for a minimum of 24 h prior to the examination to ensure an optimal response. Information sent to the patient at the time of booking should include a diet sheet explaining that abstention from caffeine includes nonconsumption of all caffeine-containing substances including coffee, tea (brewed, green, black), hot chocolate, sodas (including so-called “caffeine-free”), and energy drinks as well as chocolate and some over-the-counter analgesics and flu remedies. Patients who admit to being nonadherent at the time of examination are generally better off being rebooked following an explanation of the importance of these restrictions. There is occasional merit in continuing with the exam in patients who have come a long distance and have consumed minimal caffeine [55]; this however remains controversial [3, 7, 36]. All patients require intravenous access prior to going into the magnet room. It is preferable for access to be established in a large antecubital vein in order to be able to inject at relatively high flow rates.

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Mental Preparation of the Stress Patient One of the most important parts of the prestress preparation is the process of informed consent, which should be sought prior to every exam. This is not simply a medicolegal nicety but offers a real opportunity to coach the patient in what to expect when they are in the magnet. Patients are often nervous, and liberal use of the word “stress” rarely helps, evoking as it does an image of a sweating, palpitating figure perhaps clutching his/her chest in discomfort! In truth, the drugs used for stress perfusion are remarkably safe and generally very well tolerated. It is worth reemphasizing – to the reader – that the aim of vasodilator stress (unlike dobutamine or treadmill stress) is not to induce ischemia but rather to uncover relative differences in myocardial perfusion reserve through differential vasodilatation of normal and abnormal coronary beds. Patients may be alarmed to be told they will be “stressed” and should be reassured that the medications will not make the heart race wildly or thump heavily and that, in general symptoms, will be relatively mild. We prefer to use the term “myocardial blood flow imaging” rather than stress imaging when we consent patients since we feel this reflects a more accurate – and sedate – picture of what will take place. It is important, however, to describe the commonest side effects, which are listed in

Table 2. Mental preparation is every bit as important as physical preparation. Limited survey data suggest that stress perfusion CMR – when performed well – is overall tolerated no worse than perfusion SPECT [45].

Choice of Vasodilator Agent There are three vasodilator agents currently commercially available for stress imaging (CMR or SPECT). These are adenosine, dipyridamole, and a newer agent – not yet licensed worldwide – called regadenoson. All three are from the same family of drug, which works through alphareceptor blockade on the coronary endothelium with resulting vasodilatation. Although for each drug it is possible to find strong supporters, it is the authors’ opinion that there is little practical difference between them, with most of the touted advantages and disadvantages (Table 1) reflecting personal preferences rather than hard data. Adenosine is probably the drug used most often in stress CMR and most of the larger series have been performed using this agent. This probably reflects an early uncertainty with the safety of performing stress in the magnet environment and a concomitant wish to be able to “turn off stress” quickly – achievable due to the very short half-life of the drug. The half-life, however, also necessitates a second intravenous line since gadolinium

Table 1 Comparison of vasodilator agents [19] Dipyridamole iv infusion over 4 min Long half-life Gradual onset of symptoms Peak intensity of symptoms: usually mild Reversal usually given Very cheap almost everywhere

Adenosine iv infusion over 4 min Very short half-life More rapid onset of symptoms Peak intensity of symptoms: usually moderate Reversal rarely required Fairly cheap in most countries

Only 1 iv line required overall (gadolinium given after drug) Nonselective alpha-agonist

2 iv lines required overall (second line for gadolinium) Nonselective alpha-agonist

Requires calculation of dose based on body weight

Requires calculation of dose based on body weight

Regadenoson 30 s bolus iv injection Short half-life More rapid onset of symptoms Peak intensity of symptoms: usually mild to moderate Reversal occasionally required Expensive and not universally approved Only 1 iv line required overall (gadolinium given after drug) Selective A2a receptor agonists (relatively safe in asthma) Single pre-prepared dose regardless of body weight

Emerging Role of Stress Perfusion Cardiovascular Magnetic Resonance in the Patient with. . .

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Table 2 Common side effects of vasodilator agents Cardiovascular Facial flushing (18 %) Headache (2 %) Sweating (rare) Palpitations (rare) Chest pain (common but mild) Hypotension (