CHAPTER 16: MAGNETIC RESONANCE IMAGING OF THE HEART

Over the past 30 years, cardiovascular magnetic resonance (CMR) imaging has evolved from a technique used to acquire static images of the heart and chest into a versatile imaging modality for assessing many physiologic variables pertinent to the evaluation of patients with cardiovascular (CV) disease. CMR-based methods accurately measure left and right ventricular (LV and RV, respectively) volumes, mass, and function and are able to characterize the presence and extent of myocardial infarction (MI) and viability. Hence, they now serve as “gold standard techniques” for assessing these metrics. Increasingly, CMR enables (1) assessments of myocardial perfusion in the investigation of ischemic heart disease; (2) differentiation of the etiology of nonischemic cardiomyopathies; and (3) characterization of congenital heart syndromes, pericardial disease, and cardiac masses. The purpose of this chapter is to review the use of CMR in these clinical situations. Also, several advantages (lack of ionizing radiation, ability to image in multiple tomographic planes, high spatial, temporal and contrast resolution, and reproducibility),¹ as well as disadvantages (primarily need for availability/operator-staff experience, less feasibility in claustrophobic patients, and potential hazards associated with the magnetic field) are discussed.

For the majority of magnetic resonance imaging (MRI)–related studies, image formulation relies on principles related to signals detected from hydrogen nuclei within the body. In a strong magnetic field, these hydrogen nuclei (or protons) align and “precess” (spin) about the z-axis of the field (along the bore of the scanner). Pulse sequences or small magnetic field pulses alter this precession by delivering nonionizing electromagnetic radiation that transfers energy to (“excites”) protons and tilts them into the x-y plane to a degree determined by the flip angle. The subsequent relaxation of the protons to their original orientation within the magnetic field creates a signal that is detected by a radiofrequency receiver (or coil). Spatial variations in the magnetic field (magnetic gradients) enable identification of the physical location of these proton signals, which can then be processed into an image of their spatial distribution (Fig. 16–1). After excitation, relaxation of protons within the magnetic field is governed by the field strength and the T1 and T2 magnetic times, which are intrinsic properties of the tissue. T2* time refers to T2 after accounting for inhomogeneity of the magnetic field. Quantification (“mapping”) of these times can be performed with appropriate sequences.

Most CMR studies are performed on scanners with field strengths of 1.5 Tesla (T) or 3T. In addition to the room housing the magnet (Fig. 16–2), there is a control room located just outside the scanner room housing the computer consoles to direct the scan acquisition as well as a small equipment room housing electrical and other scanner-related equipment. For CMR studies, additional equipment is required, including that for monitoring heart rate and blood pressure, injecting intravenous contrast, and delivering intravenous medications. As images are obtained, they are typically transferred to additional computer workstations for independent image analysis and interpretation.

Recommendations for acquisition,² reporting,³ and analysis⁴ of CMR images have been recently published to guide imagers on appropriate application of these techniques.

Steady-state free precession (SSFP) cine “bright-blood” imaging forms the foundation and primary acquisition strategy for most CMR examinations.⁵ This mode of acquisition provides high contrast-to-noise between the dark myocardium and bright-blood pool⁶ and allows for the visualization of cardiac anatomy as well as atrial and ventricular contraction/relaxation. Multiple studies have demonstrated the accuracy and reproducibility of cine CMR bright-blood imaging for measuring LV volumes, ejection fraction (LVEF), and LV regional systolic function.¹ To measure LV volumes, LV mass, and LVEF, short-axis images spanning the apex to the base of the heart are acquired throughout the cardiac cycle with slice thicknesses between 6 and 8 mm, with or without 2- to 4-mm gaps, and with temporal resolution ≤ 45 milliseconds² (Fig. 16–3). Analysis is performed with computer software that uses semiautomated techniques for tracing endocardial and epicardial contours at end-diastole and end-systole and the summation of disks methods for adding volumes together from all of the short-axis slices. Measurements made with this three-dimensional (3D) data set do not require geometric assumptions and are, therefore, less prone to error than two-dimensional (2D) methods such as 2D echocardiography, especially in ventricles deformed by MI or cardiomyopathies. Interobserver and interscan reproducibility is high, allowing for reduced sample sizes in clinical trials in heart failure (HF).^7,8 Similarly, CMR is a highly reproducible technique for measurement of RV volumes because of its 3D analysis nature.⁹ The right ventricle can be measured using short-axis views or stacked axial scans; the latter improves identification of the tricuspid valve plane and correlates better with pulmonary flow measures.¹⁰

Typically, long-axis images are also obtained in standard two-, three-, and four-chamber views. Most commonly, SSFP sequences are utilized; however, gradient-echo bright-blood images may also be acquired because these images are more sensitive to detect turbulent flow in the setting of valvular obstruction or regurgitation. Stress testing can be performed with SSFP cine in multiple planes at different stages of dobutamine ± atropine infusion. These cine bright-blood images may be acquired with high spatial and temporal resolution during 6- to 10-second breath-holds (known as a segmented acquisition), or at a slightly reduced spatial and temporal resolution in “real-time” that does not require electrocardiographic gating or breath-holding. This latter technique is often used in those with arrhythmia or limited breath-holding ability.¹¹

Additional CMR methods are available for quantifying abnormalities of regional LV systolic function that may not be evident on visual inspection of the images.¹² One such technique applies radiofrequency and gradient pulses to null the myocardium at end-diastole, resulting in the placement of “tissue tags” that can be tracked through the cardiac cycle to enable assessment of myocardial deformation and measurement of myocardial strain^13,14 (Fig. 16–4). In addition to quantifying myocardial deformation, tissue tags may be used to assess pericardial adherence in the setting of possible constriction and quantify myocardial deformation in cardiomyopathies. Another newly available method to quantify regional LV function involves cine displacement encoded echoes, which enable high temporal and spatial resolution strain analyses without application of tissue tags.¹⁵ At present, these quantitative techniques are used primarily for research purposes because of their somewhat lengthy analysis times.

Morphologic imaging with “black-blood” and “bright-blood” imaging (Fig. 16–5) is useful for depicting cardiac anatomy. In spin echo black-blood images, the MRI signal of the spins from flowing blood is inverted, leaving the blood pool dark within the LV cavity. Once a staple of most CMR examinations, black-blood imaging has been largely replaced by SSFP cine imaging because of its utility for assessing cardiac structure and function during the same acquisition. It is important to note that stationary SSFP images may be acquired in 3D view over a few minutes during free breathing with both respiratory and electrocardiographic synchronization. This has the advantage of providing a 3D data set that can be manipulated and viewed in any orientation, depicting both cardiac and extracardiac anatomy (Fig. 16–6), without the need for breath-holding or contrast.¹⁶

Tissue characterization with mapping or weighted imaging using assessments of T1, T2, or T2* relaxation is increasing in importance in CMR^17,18 (Fig. 16–7). High signal on T2-weighted imaging can demonstrate myocardial edema, such as in the setting of acute MI or myocarditis. Older T2-weighted imaging approaches are prone to artifacts and more recent CMR protocols have used newer T2 mapping to overcome these limitations.¹⁹ T1 of the myocardium can be measured by mapping with a modified Look-Locker inversion recovery, or MOLLI, sequence²⁰ or shorter versions of this approach, termed shMOLLI.²¹ Native or precontrast T1 is measured before contrast infusion and then postcontrast T1 measures can be used to calculate the extracellular volume (ECV) fraction of the myocardium.²² These techniques are increasingly used to differentiate causes of cardiomyopathy.¹⁷ However, neither T1 nor T2 mapping are yet approved by the Food and Drug Administration (FDA) for clinical use. T2*-weighted imaging is sensitive to iron in the heart and can identify iron overload conditions and myocardial hemorrhage in the setting of acute MI.

Phase contrast (PC) imaging (also known as velocity-encoded cine, velocity mapping, or flow imaging) is used to display and quantify velocities and flow. It relies on the principle that precession frequency of protons is directly proportional to the velocity of a particle moving across a magnetic field gradient. If a magnetic gradient is created along the direction of blood flow, protons moving faster will be subjected to a stronger or weaker magnetic field and experience a proportional shift in their precession. Measurement of this shift, therefore, allows for the quantification of blood velocity along the direction of the gradient.²³ This is typically achieved by prescribing the acquisition perpendicular (“through-plane”) to the expected direction of flow (ie, to the ascending aorta or pulmonary artery for quantification of systemic [aortic] or pulmonary forward cardiac outputs). PC sequences typically provide two reconstructions of the acquired data: a magnitude (or anatomic) image and a phase-difference reconstruction (velocity map) where the signal intensity of each voxel is rendered proportional to its velocity (Fig. 16–8). Accuracy is highest if the limit of measurable velocities is set close to, but below, the true velocity of blood. Using these sequences, flow is calculated by integrating changes in area and velocity throughout the cardiac cycle (see Fig. 16–8), and has been validated both in vitro and in vivo,²⁴ demonstrating very high accuracy. Newer 3D sequences (also known as four-dimensional PC or four-dimensional flow imaging) have been developed that enable the quantification of velocities in all directions²⁵; however, these are not yet routinely used in clinical practice because of somewhat lengthy acquisition and processing times. Real-time PC sequences have also been developed that allow for acquisition during free breathing and without the need of electrocardiographic gating.²⁶

Perfusion imaging has evolved significantly over the past 10 to 15 years.²⁷ In general, this is achieved by imaging the first-pass of a gadolinium-based contrast agent (GBCA) through the myocardium. It can be performed at rest (eg, to identify “tumor blush”) and, for the purposes of stress testing, during vasodilator challenge to identify hypoperfusion associated with flow-limiting epicardial coronary artery stenoses.^28,29 Typically, images in three to five short-axis slices are acquired over 50 to 60 heartbeats. Images are assessed qualitatively for regions of low signal intensity consistent with hypoperfusion that encompass at least the subendocardial one-third of the myocardial wall of at least five frames or heartbeats in duration (Fig. 16–9). Comparing rest and stress imaging with late gadolinium-enhanced (LGE) imaging (see below) can differentiate perfusion defects caused by ischemia from those cause by artifacts or MI.³⁰

LGE refers to regions of scar and/or necrosis discriminated from normal tissue by prolonged retention of GBCAs as visualized on T1-weighted imaging.³¹ An inversion recovery-based pulse sequence is used to optimize the differentiation of normal dark myocardial tissue from bright areas of fibrosis or scar.³² These fibrotic areas appear bright as a result of retention of gadolinium, in turn because of increased volume of distribution as well as delayed washout of the contrast agent. LGE is considered the gold standard technique for detecting and sizing MI³¹ (Fig. 16–10). However, LGE is not unique to infarct scar and can signify any cause of fibrosis or interstitial infiltration in cardiomyopathies, many of which have a unique pattern of LGE.³³

Finally, magnetic resonance angiography (MRA), another important CV application, is typically performed using a 3D gradient echo acquisition during passage of a GBCA and is described in detail in Chap. 22.

Metallic and Electronic Devices

Although a relatively safe imaging modality, CMR does possess potential for serious and even lethal events. The magnetic field of clinical CMR scanners is 25,000 to 50,000 times stronger than that of the earth, and ferromagnetic metallic objects that come into close proximity with the field can be drawn toward the magnet in a projectile fashion. It is important to realize that the magnetic field is always “on,” even when the scanner is not being used; therefore, all personnel involved in CMR operations need to be appropriately trained, and access to the CMR room and its vicinity must be severely restricted and adequately demarcated. Only MRI-compatible devices and materials (such as injections pumps or stretchers) may enter the magnet room, and individuals need to be appropriately screened.³⁴

A CMR scanner may also pose danger to patients or personnel with implanted ferromagnetic or electronic devices. Aside from the potential for torque or pull by the magnetic field, the rapidly switching magnetic gradients can induce voltages in conducting materials, which in turn may heat surrounding tissues. In addition, depending on the sequence used, the magnetic field strength, and the specific device, changes in programming and functioning of implanted electronic devices may occur. Thus, the decision needs to be individualized for each patient to determine (1) whether the specific device is MRI-compatible and (2) at what field strength it is compatible. As a general rule, objects located in soft tissues that can be easily harmed are the greatest concern; these include the orbits and the brain (typically aneurysm clips, of which most modern ones are MRI-compatible). The vast majority of orthopedic implants are safe. Regarding devices frequently encountered in cardiac patients, safety recommendations³⁵ are summarized in Table 16–1. All current coronary stents and prosthetic valves are safe and can be imaged immediately after implantation. Many other cardiac or vascular implants are nonferromagnetic and can also be scanned at any time, or are weakly ferromagnetic and a delay of 6 weeks before MRI is recommended to allow for endothelialization. Swan-Ganz catheters contain metal and are considered unsafe. Similarly, some medication patches contain metallic foil and may need to be removed before the procedure.

Although pacemakers and implantable cardioverter-defibrillators (ICDs) have been traditionally considered absolute contraindications for CMR, an increasing body of literature indicates that it is feasible to safely scan select patients with select devices, as long as strict protocols and monitoring are followed. In the absence of such protocols, MRI with pacemakers and ICDs should still be considered unsafe.³⁴ Some MRI-compatible pacemakers and, more recently, one ICD have become available, although not all of them allow performance of CMR.

Nephrogenic Systemic Fibrosis

Although GBCAs were traditionally considered safe in patients with renal failure, an association between nephrogenic systemic fibrosis (NSF) and gadolinium use in advanced kidney disease was described in 2006. This led to a US FDA Black Box Warning related to the administration of GBCAs and NSF (a fibrosing disease primarily involving the skin and subcutaneous tissues, which can also affect internal organs). Symptoms typically include skin thickening and/or pruritus, with potential for contractures and joint immobility, and rarely, death through visceral fibrosis. The estimated incidence is 1% to 7% in those with an estimated glomerular filtration rate (eGFR) < 30 mL/min/m², and it is more common in patients on dialysis and with specific GBCAs.³⁶ GBCAs should be avoided in patients with eGFR < 30 mL/min/m² and in those with acute renal failure (where eGFR may be less accurate). Caution is recommended for those with eGFR between 30 and 40 mL/min/m² because of daily fluctuations in eGFR. For those patients on dialysis, prompt (within 2 hours) hemodialysis after the test should be considered to enhance elimination, although the benefit of this approach is unproven. Peritoneal dialysis is not considered effective.³⁶

Pregnancy and Lactation

There is no conclusive evidence that CMR can induce harm to the fetus; however, there is no solid data on its safety, either. Therefore, CMR is not recommended, although it can be performed after physician-patient discussion if the benefits are deemed to outweigh potential risks. The stage of the pregnancy plays no role in the decision.³⁴ The same applies to the use of GBCAs, which are known to cross the placental barrier and might be harmful to the fetus.³⁶ A very small amount of GBCA is excreted in the milk and it is considered safe to continue breastfeeding, although 12- to 24-hour interruption is occasionally recommended.³⁶

Other

Magnetic gradients can cause peripheral stimulation that may be perceived as tingling. They also cause loud noises, so ear protection is systematically provided. The incidence of claustrophobia precluding CMR is approximately 4%; around half of these patients will be able to undergo the test with mild sedation.³⁷

Cardiovascular Magnetic Resonance Stress Testing

Appreciation of LV myocardial ischemia has traditionally depended on identifying abnormalities of LV myocardial perfusion, wall motion, metabolism, or epicardial coronary artery blood flow after experiencing some form of stress. CMR is unique in that with a single imaging modality one can identify abnormalities of LV myocardial perfusion or wall motion in a single test with a relatively high spatial resolution and without administration of any form of ionizing radiation (Fig. 16–11). Based on multimodality appropriate use criteria, stress CMR is considered appropriate for patients with high pretest probability for coronary artery disease (CAD) or intermediate pretest probability of CAD with an uninterpretable ECG or inability to exercise.³⁸ It is also appropriate for patients with an abnormal ECG who are intermediate-to-high risk as well as those with an abnormal or uncertain exercise ECG or those with obstructive CAD of uncertain significance noted on computed tomography (CT) or invasive coronary angiography.

Imaging Suite and Environment

It is important to recognize that appropriate environmental conditions and safety procedures are required when seeking to perform CMR stress testing. Similar to stress testing environments used with other modalities, staff familiar with CV stress testing, including nursing personnel and physicians, should be present during and immediately after testing.^39,40 In regard to safety, medication carts and defibrillators should be secured outside of, but in close proximity to, the CMR scanning room, and if defibrillation during testing should be required, patients should be removed from the CMR room to deliver cardioversions. It is also important to note that specialized MRI-compatible equipment for assessing blood pressure, heart rate, oxygen saturation, and respiratory rate should be present in the MRI scanning room. Because the magnetic field alters the appearance of ST segments and T waves on the ECG once the patient enters the scanner, ECG tracings are used to monitor patients' rhythm and not to detect ST-segment changes associated with inducible ischemia. As such, many stress CMR facilities utilize near real-time image review to appreciate inducible ischemia (Fig. 16–12). As shown in Fig. 16–13, prior to CMR stress testing, a resting 12-lead ECG, intravenous access, pulse oximetry, and brachial blood pressure cuff are applied outside of the magnet room.⁴¹

In one of the largest studies of more than 1000 individuals undergoing dobutamine stress CMR, potential side effects were noted to occur in 6.4% of individuals (vasodilator stress CMR has an even better safety profile).⁴² The side effects included sustained ventricular tachycardia (0.1%); nonsustained ventricular tachycardia (0.4%); paroxysmal atrial fibrillation (AF) (1.6%); transient second-degree atrioventricular block (0.2%); marked changes in systolic blood pressure, including elevations to greater than 240/120 mm Hg (0.5%); and substantial decreases of > 40 mm Hg (0.5%). Accordingly, personnel familiar with managing these conditions should be present.

Major events during CMR stress testing are usually associated with continued infusions of pharmacologic stress agents in the setting of concurrent myocardial ischemia. As such, near simultaneous viewing of images is recommended and a high level of attention is suggested so that termination of the stress procedure can occur once evidence of ischemia is present (see Fig. 16–12).

Dobutamine Stress

For dobutamine stress testing, baseline images are acquired in three standard long-axis and short-axis views at rest (Fig. 16–14). Dobutamine (in increasing doses up to 50 μg/kg/min) and atropine are then infused to achieve a heart rate response that is 85% of the maximum predicted heart rate response for age.⁴³ Optionally at intermediate stages, repeat wall motion images may be obtained. At peak stress or at the first sign of chest pressure consistent with angina, repeat wall motion and myocardial stress perfusion images are acquired (see Fig. 16–14).^{39,40,41,42,43} The pharmacologic stress agents are then discontinued, and a recovery series of images is obtained. To interpret the test, the left ventricle is divided into 17 segments according to the American Heart Association and American College of Cardiology.⁴⁴ Throughout testing, a four-point scoring system (1 = normal, 2 = hypokinetic, 3 = akinetic, 4 = dyskinetic) is used to assess wall motion within each segment. Myocardial ischemia is identified when a deterioration of ≥ 1 in a segment score occurs during the stress test (Fig. 16–15).

As shown in Table 16–2, the sensitivity and specificity of dobutamine stress CMR for detecting greater than 50% coronary arterial stenoses with wall motion analyses alone range from 78% to 96%.⁴⁵ It is important to recognize, however, that there are several situations in which dobutamine wall motion analyses alone may underappreciate the presence of inducible ischemia and functionally important CAD. To address these outstanding issues, several investigators have advocated for the incorporation of first-pass contrast-enhanced stress perfusion at peak heart rate response during intravenous dobutamine, and the acquisition of LGE images in the recovery phase of dobutamine and atropine administration (see Fig. 16–14). In 1493 patients referred for dobutamine stress with suspected or known CAD, the simultaneous identification of LV wall motion and myocardial perfusion abnormalities was associated with an increase in the hazard ratio for future CV events.⁴⁶ The results of myocardial perfusion stress testing were most evident in those individuals with resting LV wall motion abnormalities or underlying left ventricular hypertrophy (LVH) (P =.02–.09).

These situations include those individuals with resting LV segmental wall motion abnormalities, the presence of prior MI and scar, those with LVH or concentric remodeling, and, finally, those individuals who are older and exhibit a hyperdynamic response with a decline in systolic blood pressure during testing.⁴⁷

In 278 individuals⁴⁸ aged 69 ± 8 years with preexisting or known risk factors for CAD who underwent simultaneous assessment of LV myocardial perfusion and wall motion after peak dobutamine infusion, 60% of individuals with perfusion defects indicative of myocardial ischemia exhibited no inducible wall motion abnormalities. Among these participants, myocardial oxygen demand was lower in those who had both LV wall motion and perfusion abnormalities suggestive of ischemia (P =.03). Factors associated with the presence of perfusion defects without an inducible wall motion abnormality included a reduced LV end-diastolic volume index (LV preload) or increased concentric LV remodeling. The results of these studies demonstrate the limitations of LV wall motion assessments alone when evaluating patients referred for any form of dobutamine stress examinations (CMR, echocardiography, radioisotope imaging) and point out the ability of simultaneous LV wall motion and perfusion assessments in these same situations.

Contractile Reserve and Viability

Although LGE techniques are widely used for identifying myocardial scar and thus infer viability, dobutamine stress CMR measures of LV myocardial contractile reserve remain important for assessing myocardial segments that have the potential to recover systolic function after successful epicardial coronary arterial revascularization.^49,50 Similar to the protocol utilized for myocardial ischemia, in patients undergoing dobutamine viability studies, resting images are obtained prior to initiation of stress. After baseline imaging, low-dose dobutamine infusions in the range of 7.5 to 10 μg/kg/min are administered and repeat assessments of myocardial contractility are obtained. The first study⁵¹ to publish comparisons of dobutamine stress CMR and ⁸F-fluorodeoxyglucose positron emission tomography (PET) demonstrated that dobutamine-induced wall thickening was superior to resting LV end-diastolic wall thickness alone for predicting viable myocardium. In fact, dobutamine stress CMR had similar diagnostic accuracy relative to ⁸F-fluorodeoxyglucose PET scanning.

A particular advantage of low-dose dobutamine infusions for assessing myocardial viability is that they can be administered to patients with reactive airways disease as well as those with renal dysfunction in whom the use of gadolinium may be contraindicated. In addition, there is some evidence that low-dose dobutamine stress CMR assessments of improvements in regional wall motion or radial thickening may be superior to the assessments of LGE, particularly in individuals who have intermediate presence of LGE (Fig. 16–16; see also section on remote myocardial infarction).⁵⁰

Vasodilator Stress

CMR perfusion imaging in general is accomplished after the administration of contrast agents that help to demonstrate discrepancies in LV myocardial perfusion between adjacent myocardial segments as well as absolute perfusion within a particular segment.⁵² For the most part, GBCAs are utilized because of their ability to accentuate T1 relaxivity in perfused myocardium as well as a relatively favorable safety profile for administration in those without severe chronic kidney disease.⁵³

With CMR, myocardial perfusion may be assessed qualitatively (visual inspection), semiquantitatively, or by fully quantitative methods that assess the absolute perfusion of the agent.⁵⁴ Quantitative perfusion methods have been found very accurate and to vary inversely with the degree of coronary stenosis by quantitative coronary angiography. Importantly, both quantitative as well as qualitative perfusion assessments by CMR have demonstrated very high correlations with fractional flow reserve measures using cutoff values of < 0.75.⁵⁵ Overall, those studies using qualitative assessments may require larger amounts of gadolinium contrast in the 0.1 mmol/kg range to optimize visualization, whereas quantitative analysis may be achieved with much lower doses, such as 0.05 mmol/kg. Although quantitative and qualitative analyses have similar accuracy on a per-patient basis, quantitative analysis of perfusion reserve identifies the extent of myocardial ischemia more accurately.⁵⁶

Although intravenous adenosine or dipyridamole has traditionally been administered to accomplish vasodilator stress, regadenoson has been utilized in the CMR environment as well. This agent is beneficial for the study of individuals with obstructive or reactive airways disease in that regadenoson will enhance endothelial independent vasodilation of the coronary microcirculation but not precipitate bronchial constriction associated with lung disease.⁵⁷

The stress perfusion protocol includes a stress perfusion assessment, followed by evaluation of LV wall motion, rest perfusion, and LGE identification of myocardial injury/fibrosis. Utilizing this methodology, the sensitivities and specificities for identifying flow-limiting coronary arterial stenoses when compared to contrast coronary angiography have both exceeded 90%.⁵⁸ The high spatial resolution of this technology enables identification of subendocardial infarcts that can be distinguished from small areas of subendocardial hypoperfusion related to reduced myocardial microcirculatory blood flow (Fig. 16–17) resulting from flow-limiting epicardial coronary arterial stenoses. In addition, this particular technique is useful for identifying inducible ischemia in those individuals with preexisting concentric LVH or remodeling, reduced LVEF, or female gender (when body habitus can impede acquisition with other methodologies).

Across several meta-analyses, the overall sensitivity and specificity of CMR vasodilator perfusion tests for identifying flow-limiting coronary artery stenoses were 91% and 81%, respectively. In addition, in a relatively large meta-analysis,⁵⁹ reporting on 4721 vessels in 2048 patients, CMR vasodilator stress performed similarly to CT and PET and better than single-photon emission computed tomography (SPECT) or echocardiography using pooled sensitivity and specificity analyses for identifying functionally important CAD (Table 16–3). When compared with fractional flow reserve measures, CMR has been shown in multicenter initiatives to compare favorably, and perhaps superiorly, to existing radioisotope and radionuclide techniques.⁶⁰ Several comparative study results have suggested that CMR perfusion imaging could realistically be used as an alternative (with superior results) to SPECT imaging. This was most convincingly demonstrated in the recent single-center Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease (CE-MARC) study that directly compared CMR stress perfusion and LGE with SPECT.⁶¹ In this study, CMR was found to have higher sensitivity and similar specificity to SPECT, using angiography stenosis severity as a study end point (Fig. 16–18). In addition, abnormal CMR stress perfusion abnormalities correlate with fractional flow reserve assessments obtained invasively.⁵⁵

Prognosis

Beyond the identification of flow-limiting coronary stenoses or inducible ischemia, both CMR myocardial perfusion as well as CMR dobutamine wall motion stress are useful to determine cardiac prognosis.⁶² In populations with chest pain presenting to the emergency department, CMR perfusion exhibits a sensitivity of 100% and specificity of 93% for predicting subsequent death from MI or detection of coronary stenosis after one year of follow-up.⁶³ In another study,⁶⁴ both adenosine myocardial perfusion as well as dobutamine CMR wall motion were evaluated in 513 patients subsequently followed for up to 3 years. Stress CMR using myocardial perfusion or wall motion analyses contributed to the incremental value over traditional risk factors for identifying those with an adverse cardiac prognosis. Normal perfusion studies were associated with an event rate of 0.7% at 2 years, whereas an abnormal study exhibited an event rate of 12.2% over the same time period. In a multivariable analysis including other risk factors for cardiac events, detection of perfusion abnormalities was associated with a 10-fold risk of future hard events. Similar results were found for dobutamine wall motion assessments.

A particular advantage for utilizing stress CMR for assessing myocardial perfusion or LV wall motion relates to the prognostic utility in women.^65,66 As shown in Fig. 16–19, stress CMR exhibits very high spatial resolution and fewer artifacts for imaging women relative to radioisotope techniques and, importantly, CMR stress does not involve ionizing radiation exposure to breast tissue.

In a meta-analysis totaling 14 studies involving 12,178 individuals,⁶² the negative predictive value for nonfatal MI and cardiac death of a normal CMR was 98.1% (with a 95% confidence interval of 97.3 to 98.8) during a main follow-up of 25.3 months. The corresponding annualized event rate after a negative test was 1.03%. These results demonstrate that CMR exhibits a relatively high negative predictive value for adverse cardiac events, and the absence of inducible perfusion defects or wall motion abnormalities demonstrate a similar ability to identify low risk patients with known or suspected CAD.⁶²

Health Care Expenditures and Utilization

Although clear algorithms for diagnosis and treatment of patients with chest pain at varying levels of risk for acute coronary syndrome (ACS) exist, there are less well-delineated criteria for those individuals presenting with chest pain at intermediate risk for ACS. An important series of studies from Miller and colleagues^67,68,69 has demonstrated the utility of stress CMR in chest pain observation units associated with emergency departments. Three recent studies involving more than 300 participants randomized to usual cardiac care versus a stress CMR implemented through chest pain observation units examined those presenting with intermediate-risk chest pain (preexisting CAD and MI, ECGs with T-wave inversions without ST-segment depression exceeding 3 mm or ST-segment elevation exceeding 1 mm). Participants managed through the CMR-guided pathways experienced on average a reduction in the cost of the initial visit of $588 and reduction of $1641 over the ensuing year (Fig. 16–20).^67,68,69 When examined further, the decreased utilization and costs associated with managing the patients using CMR results was related to fewer return visits to the emergency department, cardiac catheterizations, and percutaneous coronary artery revascularization procedures. Overall, patients experienced no difference in the 30 days or 1-year occurrence of MI or cardiac death. These important results highlight the potential benefits of using CMR stress perfusion for identifying those individuals presenting to the emergency department with chest pain at intermediate risk for ACS and in need of hospitalization, as opposed to those who could be safely discharged to home.

Myocardial Tissue Characterization

Today, perhaps the most widely used imaging method for identifying myocardial injury and fibrosis associated with MI is through CMR-based assessments of LGE.⁷⁰ LGE has several important uses in the setting of patients with suspected CAD. These include identification of the extent of acute and remote MI, prediction of recovery of myocardial contractility after successful coronary artery revascularization in chronic ischemic heart disease, characterization of prognosis, visualization of cardiac thrombus or microvascular obstruction and, when combined with T2 imaging methods, localization of the area of myocardial salvage.

Acute Myocardial Infarction

Triphenyltetrazolium chloride (TTC) histopathologic staining has been utilized to document the accuracy of the spatial extent and localization of LGE as it relates to infarcted myocardium.⁷¹ In canine models, there have been high correlations between LGE and TTC-stained measures of infarcted myocardial segments (Fig. 16–21). The relatively high spatial resolution of LGE images enhances its sensitivity for detecting MI. CMR may be used to identify micro infarcts because of relatively small epicardial coronary artery branch occlusions or embolization of distal vessels related to percutaneous coronary artery revascularization procedures.⁷² CMR has been shown to be more sensitive than both SPECT and PET imaging for detecting small infarcts.⁷³ In a large multicenter clinical trial of 282 patients, the sensitivity for detecting acute MI was 99%. Transmural extent of LGE can additionally predict the likelihood of functional recovery of stunned myocardium because there is an inverse relationship between transmurality and recovery of function.⁷⁴

Remote Myocardial Infarction

In patients evaluated chronically (months to years) after MI, the assessment of transmural extent of infarction has also been shown to identify the likelihood of functional recovery of systolic thickening after percutaneous coronary artery revascularization procedures.⁷⁵ For individuals with no LGE, recovery of function of resting segments with akinesis can approach 80%. Conversely, in individuals with greater than 50% transmural extent of infarction, the likelihood of recovery of systolic thickening after coronary artery revascularization falls below 10%.

One potential difficulty in using this method to assess potential for recovery of systolic thickening occurs when the transmural extent of infarction ranges between 1% and 50%. In these situations, there is approximately a 40% to 60% chance of recovery of systolic thickening. As shown in studies by Wellenhoeffer and colleagues, the ability to identify those segments with a potential for systolic thickening after revascularization improves to nearly 90% through the identification of contractile reserve with low dose intravenous dobutamine (see Fig. 16–16).⁵⁰

Microvascular Obstruction

In the setting of acute MI, the coronary artery microcirculation can be damaged to an extent such that no gadolinium may be temporarily delivered to specific areas within an infarct zone.^76,77 These areas have been shown histopathologically to be associated with microvascular obstruction caused by plugging of the small arterioles with thrombotic debris.^76,77 The characteristic image finding (Fig. 16–22) indicates a very dark central core nested within a relatively bright LGE region of myocardium consistent with acute/subacute necrosis. Often on the cine wall motion images, these areas display marked hypokinesis or akinesis. Postcontrast cine imaging can also be useful to differentiate microvascular obstruction from thrombus (see Cardiac Masses, below).

It is important to recognize that the presence of microvascular obstruction is associated with an adverse cardiac prognosis and very little opportunity for recovery of systolic thickening longitudinally over time.⁷⁸ In addition, the presence of microvascular obstruction has also been associated with adverse LV remodeling and worse patient outcomes.^78,79

Myocardial Area at Risk and Salvageable Myocardium

In patients presenting with acute chest pain syndromes, it is important to recognize that edema imaging utilizing either T2-weighted or T2 mapping sequences may be combined with LGE techniques to identify the area at risk and salvageable myocardium as well as to differentiate stress-induced cardiomyopathies from actual MI.^80,81

Prior to the administration of contrast, T2-weighted imaging or T2 mapping can be used to characterize the presence of myocardial edema. Abdel-Aty and colleagues⁸² have demonstrated that edema imaging depicts acute ischemic injury often within the first 30 minutes from abrupt coronary artery occlusion and even before the development of LGE. Therefore, in the setting of an acute infarction, bright signal observed in T2 imaging techniques predicts the maximal area of myocardium that is at risk for necrosis.

Myocardial salvage relates to a term that defines the difference between the area at risk subtracted from the extent of necrosis as determined with LGE.^80,81 As shown in Fig. 16–23, edema involves the entire area of the myocardial wall, whereas the transmural spread of necrosis is variable and is identified with LGE imaging. In the situation where abrupt return of antegrade coronary flow is established or extensive collateral flow is present, the degree of myocardial salvage can be readily identified. Importantly, this region represents an area of risk of reinfarction in patients in whom inadequate coronary artery blood flow recurs.

Intramyocardial Hemorrhage

One complication associated with acute MI is the development of intramyocardial hemorrhage.⁸³ CMR is well suited to identify intramyocardial hemorrhage utilizing a combination of T2-weighted and T2*-weighted imaging, as well as LGE. T2*-weighted imaging is very useful to identify the presence of hemoglobin degradation products. These products produce a low signal intensity on T2*-weighted images. In a series of 98 individuals sustaining an MI, approximately one-fourth experienced hemorrhagic infarcts that were in turn associated with infarction transmurality, a larger MI size, and reduced LVEF.⁸³ In addition, those with myocardial hemorrhage experienced a greater increase in LV end-systolic volume 4 months after the infarct relative to those without evidence of myocardial hemorrhage. These data suggest that the presence of myocardial hemorrhage identified by T2*-weighted imaging during CMR may predict adverse LV remodeling.

Overview

CMR is an extremely useful technique in the assessment of the patient.^1,5,84 The fact that SSFP cine CMR is considered the “gold standard” for measurement of LV and RV structure and function is especially important in cardiomyopathies. The pattern of LGE can be quite useful in differentiating causes of cardiomyopathies³³ (Fig. 16–24). T2-weighted imaging can be used to demonstrate myocardial edema, such as in acute myocarditis.⁸⁵ T1 mapping techniques are being applied to help in the differential diagnosis of cardiomyopathies; some have characteristically high native T1⁸⁶ as well as high ECV fraction.⁸⁷ Native (or non-GBCA) T1 mapping is especially useful in patients with severe chronic kidney disease and risk of NSF.

Ischemic Cardiomyopathy

The first step in the evaluation of the patient with new-onset HF is to establish the underlying etiology and, importantly, to exclude ischemic heart disease as a potentially reversible cause. CMR is considered an appropriate technique for the evaluation of patients with new-onset HF.⁸⁸ The approaches to evaluating for ischemia are discussed in the preceding section of this chapter. In the setting of HF, stress CMR is considered appropriate in evaluating an ischemic cause.⁸⁸ SSFP cine imaging demonstrates LV dilatation and segmental LV dysfunction in a coronary distribution pattern. The presence of LGE in a coronary distribution can support the diagnosis of underlying CAD (Fig. 16–25), but its absence does not rule it out, because patients with extensive hibernating myocardium may not have LGE.⁸⁹ In a study by Soriano and colleagues of 71 patients with new-onset HF and systolic dysfunction, the sensitivity of the infarct pattern of LGE for ischemic cardiomyopathy, as defined by the presence of obstructive CAD, was 81%, whereas the specificity was 91%.⁸⁹ Patients without obstructive CAD may have evidence of LGE in an infarct pattern because of transient thrombotic occlusion of a nonobstructive artery, embolization, or spontaneous coronary dissection and, thereby, may be misclassified. This finding was noted in 13% of 63 patients with the diagnosis of dilated cardiomyopathy (DCM) with chronic HF.⁹⁰

The presence and amount of LGE is prognostically important in the setting of CAD. One study of 195 patients found that the presence of any LGE was associated with an 8.3 hazard ratio for major adverse cardiac event (MACE) and a 10.9 hazard ratio for cardiac mortality.⁹¹ In another study of 857 patients followed for 4.4 years on average, a scar index based on LGE was an independent predictor of all-cause mortality or cardiac transplantation, in addition to other well-known risk factors, including LVEF and age.⁹² The presence of scar is also a marker of poor response to cardiac resynchronization therapy (CRT), especially when the scar is located within the LV inferolateral wall at the site of the placement of the pacing lead within the cardiac vein.^93,94 CMR is considered an appropriate imaging examination in the evaluation of viability and in the evaluation of candidacy for CRT.⁸⁸

Dilated Cardiomyopathy

Cine imaging in DCM generally demonstrates global LV dysfunction or regional dysfunction in a pattern inconsistent with a territory subserved by a single epicardial coronary artery. The majority of patients with HF without obstructive CAD have no evidence of LGE.⁹⁰ As mentioned above, a minority of patients (13%) have LGE in an infarct pattern and may be misclassified as nonischemic.⁹⁰ Approximately one-fourth of patients with DCM will have evidence of mid-wall fibrosis⁹⁰ (Fig. 16–26). This may represent the chronic healing phase of myocarditis. In a study of 472 patients with DCM followed for 5.3 years, the 142 patients with mid-wall fibrosis had a hazard ratio of 3.0 for all-cause mortality and 5.2 for a composite end point of sudden cardiac death (SCD) and aborted SCD.⁹⁵ A study of 65 patients with DCM and LVEF ≤ 35% showed that the presence of LGE was associated with an eight-fold increase in HF, appropriate ICD firing, and cardiac death.⁹⁶ The presence of mid-wall fibrosis is also an independent predictor of mortality and morbidity of patients with DCM undergoing CRT.⁹⁷ In fact, in this study of 97 patients with DCM and 161 patients with ischemic cardiomyopathy, DCM patients with mid-wall fibrosis had a similar outcome to those with ischemic disease.⁹⁷ Thus, as with ischemic cardiomyopathy, the presence of fibrosis/scar is a marker of adverse outcome and lack of response to device therapy.

Hypertrabeculation can be seen in patients with DCM. A prospective CMR study of 162 patients with this disorder measured the amount of noncompacted myocardium relative to compacted myocardium.⁹⁸ Whereas LVEF and LGE were independent predictors of MACE-free survival, the amount of noncompacted myocardium had no effect above and beyond traditional factors (eg, LVEF) associated with adverse CV events.

Myocarditis

A typical patient with acute myocarditis presents with chest pain, modest troponin elevation, and little or no evidence of angiographically detectable stenoses within epicardial coronary arteries. Cine imaging can demonstrate normal LV systolic function, regional dysfunction, or global dysfunction. The finding of LGE in the midwall and subepicardium of the left ventricle is characteristic of viral myocarditis and has been validated against histopathology³³ (Fig. 16–27). The presence of LGE was shown to have a hazard ratio of 8.4 for mortality and 12.8 for cardiac mortality, independent of clinical symptoms in a study of 222 patients followed for 4.7 years.⁹⁹ Older studies suggested that early postcontrast T1-weighted enhancement of the myocardium could be a marker of inflammation in myocarditis.¹⁰⁰ In addition, T2-weighted imaging demonstrated that myocardial edema can be a diagnostic sign. The Lake Louise consortium in 2009 suggested that positivity of two of three techniques (early enhancement ratio, LGE, and/or increased T2 signal) may be a good diagnostic approach.¹⁰¹

However, the early enhancement ratio has lost favor because of lack of reproducibility, and T2-weighted imaging is being replaced by more quantitative T2 mapping. In addition, T1 mapping, both native and with contrast for measurement of ECV, is increasingly being used to make the diagnosis (Fig. 16–28). A study of 50 patients with suspected acute myocarditis and 45 age-matched controls showed that patients had higher T2 signal intensity ratios and native myocardial T1 than controls.⁸⁷ In fact, a T1 cutoff of 990 milliseconds at 1.5T demonstrated a sensitivity, specificity, and diagnostic accuracy of 90%, 91%, and 91%, respectively. A combination of these techniques may more precisely identify acute myocarditis. In one recent study of 104 patients and 21 controls, a stepwise approach using LGE and myocardial ECV > 27% demonstrated an overall accuracy of 90%.¹⁰² Diagnostic accuracy of the different techniques may depend on timing of clinical presentation. A study of 61 patients with acute and 67 with chronic myocarditis showed that for acute myocarditis, diagnostic accuracy of native T1 was 99% as compared to 86% for LGE alone and 72% for increased T2-weighted signal.¹⁰³ In chronic myocarditis, LGE alone performed better than T1 mapping (94% vs 84% accuracy), but the combination of the two techniques performed even better, with a 98% overall accuracy.

Hypertrophic Cardiomyopathy

More sensitive than echocardiographic techniques, CMR can identify unusual sites of hypertrophy, particularly involving the cardiac apex.¹⁰⁴ It is the most accurate way of measuring LV mass in hypertrophic cardiomyopathy (HCM), which is important because higher LV mass is associated with worse outcome.¹⁰⁵ Similarly to echocardiography, CMR is useful to identify systolic anterior motion of the mitral valve and characterize both LV outflow gradients and the severity of mitral regurgitation.

In addition to defining myocardial mass and assessing cardiac or valvular function, CMR can assess myocardial fibrosis. Approximately two-thirds of patients with HCM exhibit LGE with diffuse or “patchy” myocardial involvement, particularly at the RV septal insertion sites and in those walls with the greatest amount of hypertrophy (Fig. 16–29).

A number of studies have examined the relationship between the presence of LGE and outcome in HCM. Two prospective studies showed that LGE was associated with an increased risk of CV events. One study followed 243 HCM patients for 3 years for all-cause and cardiac mortality.¹⁰⁶ LGE was seen in 67% and demonstrated an odds ratio of 5.5 for all-cause mortality and 8.0 for cardiac mortality. Another group followed 217 patients for 3 years for a composite end point including CV death, unplanned CV admission, sustained ventricular tachycardia or ventricular fibrillation, or appropriate ICD discharge.¹⁰⁷ Sixty-three percent had LGE, which was associated with an odds ratio of 3.4 for the primary end point. A meta-analysis of 1063 patients pooled from four studies, including these latter two, followed for an average of 3.1 years, demonstrated that the presence of LGE had an odds ratio of 2.9 for cardiac death, 5.7 for HF death, and 4.5 for all-cause mortality, but only a trend for SCD.¹⁰⁸

These studies treated LGE in a binary fashion, but more recently the extent of LGE has been shown to add discriminatory value. A single-center study of 711 patients followed for 3.5 years showed that 65% of patients had LGE and the extent was a univariate predictor of SCD risk but was not independent of LVEF.¹⁰⁹ A larger four-center study of 1293 patients followed for 3.3 years showed that LGE ≥ 15% of LV mass was associated with an independent two-fold increase in SCD event risk after adjusting for standard risk factors and LVEF.¹¹⁰ In addition to the amount, the location and/or pattern of LGE may be more predictive of adverse outcome than the presence of LGE alone. The ongoing National Institutes of Health–funded natural history study HCMR-Novel Predictors of Prognosis in Hypertrophic Cardiomyopathy (NCT01915615) using CMR, genetics, and biomarker evaluation of 2750 patients with HCM is likely to offer further insight into identifying risk markers.¹¹¹

Amyloidosis

In addition to the classic findings of biventricular hypertrophy and biatrial enlargement, and the possible presence of a pericardial effusion in cardiac amyloidosis, the existence of amyloid protein in the myocardial interstitium is associated with characteristic patterns of LGE resulting from abnormal gadolinium kinetics in the infiltrated myocardium¹¹² (Fig. 16–30). In 33 patients with diastolic dysfunction and features concerning for amyloid,¹¹³ the pattern of circumferential subendocardial LGE had a sensitivity of 80% and specificity of 94% for identifying endomyocardial biopsy evidence of cardiac amyloid. When the volume of distribution of gadolinium is quantified using serial measures of T1 in the myocardium after gadolinium contrast infusion, it is markedly increased compared to normal controls.¹¹⁴ In addition, the native T1 of myocardium is significantly longer in patients with amyloidosis as compared to that in age-matched individuals without amyloidosis¹¹⁴ or in those with LVH resulting from aortic stenosis.¹¹⁵

CMR is increasingly used to discriminate light chain (AL) amyloidosis from the transthyretin (ATTR) form of the disease. One group examined native T1 mapping in 85 ATTR patients and 79 AL patients compared with 52 normal subjects and 46 patients with HCM.¹¹⁶ Compared to those with HCM, those with AL disease demonstrated the highest native T1, followed by those with ATTR, although the area under the receiver operating curve was similar for both forms of amyloidosis (0.84). The potential utility of native T1 is critically important because many amyloid patients have concomitant renal dysfunction and are not candidates for gadolinium caused by NSF concerns. Another study compared LGE findings in 46 patients with biopsy-proven AL and 51 with ATTR amyloidosis.¹¹⁷ LGE was much more extensive in ATTR, with 90% demonstrating transmural LGE compared to only 37% in AL. These investigators developed an LGE scoring system that differentiated the two types with 87% sensitivity and 96% specificity.

LGE in amyloidosis has prognostic utility as well. In a study of 90 patients with suspected cardiac amyloidosis compared to 64 patients with hypertensive LVH, diffuse LGE predicted mortality with a hazard ratio of 5.5 in the amyloidosis patients.¹¹⁸ A cohort of 250 patients (122 with ATTR, 9 asymptomatic mutation carriers, and 119 with AL) was followed for 2 years after LGE CMR.¹¹⁹ A transmural pattern of LGE predicted death with a hazard ratio of 5.4 and remained independently predictive after adjustment for biomarkers and LV size and function. In a population of 100 patients with AL amyloidosis, ECV > 0.45 was also predictive of mortality, with a slightly lower hazard ratio of 3.8.¹²⁰

Sarcoidosis

CMR can readily identify characteristic features of cardiac sarcoidosis, including biventricular dilation and dysfunction. There is a variable pattern of LGE seen with cardiac sarcoid with a classic pattern of mid-wall or epicardial LGE, but it can also present with subendocardial or transmural enhancement in almost any distribution (Fig. 16–31). One study of CMR in 58 patients with biopsy-proven pulmonary sarcoid found 19 patients with evidence of LGE, mostly in the basal and lateral myocardium, a higher prevalence than identified by standard Japanese Ministry of Health (JMH) guidelines.¹²¹ Another study of 81 patients with extracardiac sarcoidosis followed on average for 21 months demonstrated a two-fold higher rate of cardiac involvement by CMR than by JMH guidelines,¹²² suggesting the JMH criteria may be insensitive. Compared to those without, patients with LGE in the latter study had a nine-fold higher incidence of adverse events, although the difference did not reach statistical significance due to low numbers. In addition, T2 mapping may have a role in delineating activity of sarcoidosis. In a study of 28 patients with sarcoidosis, regions of LGE demonstrated decreased T2, which may reflect an inactive phase of the disease.¹²³

With longer follow-up, LGE in sarcoidosis is demonstrating prognostic significance. In a study of 155 patients with systemic sarcoidosis followed for 2.6 years, the presence of LGE was associated with a hazard ratio of 31.6 for death, aborted SCD, and appropriate ICD discharge.¹²⁴ In fact, no patient without LGE died of a cardiac cause despite LV dilatation and dysfunction. In another study of 106 patients with extracardiac sarcoid, cardiac involvement was identified by the presence of typical patterns of LGE in 32 patients. The presence of cardiac sarcoidosis/LGE was associated with more SCD and ventricular arrhythmias or appropriate ICD discharge.¹²⁵

Anderson-Fabry Disease

Early CMR studies of Anderson-Fabry disease showed LGE related to the extent of LVH, typically located in the basal inferolateral wall and in the midwall or subepicardium.¹²⁶ T1 mapping in Anderson-Fabry disease demonstrates reduced native T1 in patients with phenotypic LVH compared to other hypertrophic diseases,¹²⁷ and an intermediate reduction in native T1 before the onset of hypertrophy.¹²⁸ In the LVH-negative individuals, echo measures of systolic and diastolic function were impaired. CMR has been used to follow regression of LVH with enzyme replacement therapy in this disorder.¹²⁹

Chagas Disease

A study of 51 patients with Chagas disease and CMR demonstrated cardiac involvement.¹³⁰ The patient group included 15 asymptomatic patients, 26 with clinical disease, and 10 with clinical disease and ventricular tachycardia. There was a stepwise increase in the prevalence of LGE in these groups (20%, 85%, and 100% respectively), and LV function was reduced proportionately to the extent of LGE.

Noncompaction Cardiomyopathy

The accurate diagnosis of left ventricular noncompaction cardiomyopathy (LVNC) by noninvasive imaging can be quite difficult because of substantial overlap between cardiac conditions. One group proposed CMR criteria of noncompacted to compacted layer thickness ratio of 2.3 to 1¹³¹ and demonstrated a sensitivity of 86% and 99% in a study of 177 patients with and without cardiac disease (Fig. 16–32). When using these criteria, up to 43% of individuals who undergo CMR as part of screening studies, such as the Multi-Ethnic Study of Atherosclerosis, can meet imaging criteria.¹³² Thus, ECG criteria and clinical criteria of symptomatic HF and LV dysfunction on imaging may need to be included to improve the specificity of diagnosis. Another group proposed a set of criteria in a study of patients with LVNC compared to those with DCM, HCM, and structurally normal hearts.¹³³ They found that a trabeculated LV mass greater than 20% of the total LV mass was 94% sensitive and specific for the diagnosis of LVNC. LGE may be seen as well in LVNC, and its presence is specific but not sensitive in making the diagnosis.¹³⁴

Iron Overload Cardiomyopathy

T2*-weighted imaging allows the measurement of cardiac iron deposition because there is an inverse relationship between T2* and iron concentration.¹³⁵ This mode of imaging has become quite important in iron overload states such as hemochromatosis and β-thalassemia major.¹³⁶ A T2* < 10 milliseconds is an important predictor of clinical HF¹³⁷ (Fig. 16–33). This application has been carefully validated and performed in a large number of international sites. Clinical trials of chelation therapies have used T2* imaging to track reductions in cardiac iron and concomitant improvements in LVEF.¹³⁸

Takotsubo Cardiomyopathy

Takotsubo or stress cardiomyopathy is a clinical syndrome characterized by chest pain and ECG changes that mimic an acute MI, generally occurs in older patients (more often women), and is typically provoked by underlying emotional or physical stress. Coronary angiography generally demonstrates no or minimal coronary atherosclerosis. Findings on CMR that corroborate this diagnosis are characteristic wall motion abnormalities (ballooning) involving the apex (82%), although midventricular (17%) and basal variants (1%) are also described.¹³⁹ In addition, there is generally no LGE but evidence exists of myocardial edema in the territory of the wall motion abnormality on T2-weighted imaging and/or T2 mapping (Fig. 16–34). Follow-up CMR generally shows normalization of LV function and inflammatory imaging markers.

Arrhythmogenic Right Ventricular Cardiomyopathy

CMR is an important adjunct in making the diagnosis of arrhythmogenic RV cardiomyopathy.¹⁴⁰ Diagnostic findings in this disease include RV dilatation and global or regional dysfunction including focal RV systolic bulging or aneurysm as defined by SSFP cine imaging, and are carefully assessed to meet specifications of the ARVC Task Force for the diagnosis of right ventricular dysplasia/cardiomyopathy.¹⁴⁰ The finding of fatty infiltration within CMR images of the RV free wall is not part of the diagnostic criteria because this is a nonspecific finding. In certain cases, LGE of the RV free wall can be seen,¹⁴¹ although this can be difficult to identify definitively because of the thin RV wall in this disorder.

Heart Failure with Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is a heterogenous syndrome that is thought to cause up to 50% of cases of HF. A recent CMR study demonstrated that patients with HFpEF with invasively confirmed elevation in pulmonary capillary wedge pressure had a lower postcontrast T1 time corresponding with myocardial fibrosis.¹⁴² However, ECV is less confounded than postcontrast T1 time by factors including imaging time after contrast and contrast dose.¹⁸ One study demonstrated that patients with HFpEF had increased ECV as compared to systolic HF and controls, and demonstrated a correlation between ECV and LV filling rate as a marker of diastolic dysfunction.¹⁴³ Studies such as these will help clarify the potential role of CMR in the diagnosis of HFpEF.

CMR imaging of pericardial disease in general is considered appropriate,^1,144 with evaluation for pericardial constriction being the most common indication.

Constrictive Pericarditis

The hallmarks of this disease are increased pericardial thickness, pericardial inflammation, and ventricular interdependence. The pericardium can be visualized and measured in a number of sequences, although T1-weighted black-blood imaging is usually the standard,¹⁴⁵ where the pericardium appears as a hypointense linear structure surrounded by hyperintense fat layers (Fig. 16–35A). Although normal pericardial thickness is less than 1 mm, on CMR, 1 to 3 mm is considered normal because of limitations in spatial resolution,¹⁴⁵ and a thickness of 4 mm or more is considered abnormal.² Pericardial thickening may be focal or diffuse. It is important to realize that pericardial thickness may not be accurately quantified in the presence of an effusion (both are hypointense on black-blood imaging), that constriction can occur with normal pericardial thickness, and that increased thickness is not synonymous with constriction.

Pericardial inflammation and edema may be detected with T2-weighted imaging.¹⁴⁶ More commonly, inflammation is evaluated with postcontrast enhancement on T1-weighted black-blood imaging or standard LGE sequences (Fig. 16–35B). On histological validation, pericardial LGE is associated with chronic inflammation, granulation tissue, neovascularization, and fibroblast proliferation, while patients with absent LGE have thinner pericardium with more fibrosis and calcification.¹⁴⁷ Importantly, the presence of extensive LGE may identify a subgroup of patients in whom constrictive pericarditis can revert with anti-inflammatory therapy.^148,149

Beyond anatomy and tissue characterization, CMR can provide information on the presence of constrictive physiology. Ventricular interdependence during respiration is studied with the use of real-time cine images. Marked inspiratory septal flattening can be seen in constriction (Fig. 16–35C and D) (and occasionally in the presence of significant tricuspid regurgitation), which can be helpful in the diagnosis and in the differentiation from restrictive cardiomyopathy.¹⁵⁰ Abnormal interdependence is typically assessed visually, although quantitative approaches have been proposed.¹⁵¹ The availability of real-time PC imaging has enabled the study of respiratory variation in mitral and tricuspid inflow as another diagnostic tool.¹⁵²

Additional features of pericardial constriction include tubular-shaped ventricles, abnormal diastolic septal bounce, atrial enlargement, dilated inferior vena cava and/or suprahepatic veins, and pleural or pericardial effusions. Application of myocardial tagging techniques often demonstrates lack of slippage between pericardium and epicardium, consistent with adherence. Pericardial calcification is not well seen on CMR and is better characterized with CT.¹⁴⁵

Other Pericardial Diseases

Acute pericarditis can be diagnosed with CMR based on the presence of pericardial T2 hyperintensity and/or LGE¹⁵³ (Fig. 16–36). Using LGE to monitor inflammation, CMR-guided therapy has been associated with fewer relapses and decreased need for steroid therapy in recurrent pericarditis.¹⁵⁴ CMR is rarely used specifically for the evaluation of pericardial effusion or tamponade. However, CMR can depict loculated or small effusions that may be difficult to detect with ultrasound¹⁴⁵ and may also provide some gross fluid characterization. Uncomplicated fluid (transudate) is typically hyperintense on cine imaging and hypointense on T1-weighted black-blood imaging (although simple motionless fluid is also hyperintense on T2-weighted imaging, pericardial fluid often moves during the cardiac cycle and may be nulled like circulating blood). Exudates and (recent) hemorrhagic effusions become progressively less intense on cine images and more intense on T1-weighted imaging¹⁴⁵ (Fig. 16–37). Chylous effusions are particularly hyperintense on T1-weighted imaging.¹⁵⁵ Pericardial masses can also be characterized with CMR (see Cardiac Masses). Finally, congenital abnormalities, such as pericardial diverticuli and partial or complete absence of the pericardium, can also be depicted. The diagnosis of congenital pericardial absence relies on marked levorotation and hypermobility of the cardiac apex, together with lung interposition in the aortopulmonary recess.¹⁵⁶

The evaluation of valvular heart disease is not typically a primary indication for CMR, given the advantages of echocardiography: portability, high temporal and spatial resolution, excellent quantification of blood velocities, and reliable investigation of valve prostheses. Therefore, valve assessment in CMR is more often integrated into a protocol performed for a different reason such as the study of cardiomyopathy, aortic abnormalities, or congenital heart disease. Validation of CMR for valvular evaluation is somewhat limited, particularly for right-sided valves, although there is mounting evidence of not only diagnostic but also prognostic value (see below). Yet, as recommended by current practice guidelines, CMR is the best alternative to ultrasound in cases of discordant test results or when echocardiographic images are of limited quality.^1,144,157 The main advantage of CMR for assessing valvular heart disease is the ability to quantify the severity of stenosis and the magnitude of valvular regurgitation. Beyond one-time or serial determination of the impact of valvular abnormalities on chamber size and function¹⁵⁷ or the presence of concomitant myocardial fibrosis, the mainstays of valve assessment with CMR are the evaluation of valve morphology and function with cine sequences as well as flow velocities with PC imaging. Although the feasibility of prosthesis assessment (particularly biological) with CMR has been reported,¹⁵⁸ artifacts from the metallic components of these devices often limit the ability to assess prosthetic leaflet mobility.

High-resolution cine images are typically obtained in standard or modified long-axis views as well as oblique planes parallel to the valvular annulus of interest,² the latter being particularly useful to demonstrate morphological variants¹⁵⁷ (Fig. 16–38). Valvular calcification can be depicted as persistently dark regions on the valvular apparatus, although CT is typically superior (see Chap. 17). The role of CMR in the evaluation of endocarditis is also limited because vegetations may be difficult to visualize due to their motion and the fact that they appear as signal voids (similar to calcification) on CMR (see Cardiac Masses).

As mentioned in the section on Techniques, flow turbulence leads to intravoxel phase dispersion and signal loss; thus, both stenotic and regurgitant jets appear dark on cine images (Fig. 16–39A). Although useful to identify the presence of a jet, the extent and appearance of jets are dependent on the sequence used, and thus one must take caution in using the size or extent of a CMR signal void to assess the severity of valvular stenosis or regurgitation.¹⁵⁹ Moreover, because dephasing is secondary to flow turbulence, laminar jets such as those observed with free regurgitation may be inconspicuous on cine imaging.

Valvular Stenosis

There are two potential approaches for the evaluation of stenosis severity with CMR. The first one relies on the quantification of blood flow acceleration through the valve using PC imaging. Transvalvular gradients can be obtained by applying a modified Bernoulli equation (Fig. 16–40A), and valve area can be measured using the continuity equation in a fashion similar to that used in Doppler ultrasound (see Chap. 15). Validation against echocardiography has been performed for both the mitral¹⁶⁰ and aortic¹⁶¹ valves. It is important to note that CMR measures of peak velocity may be underestimated if the imaging plane is not located at the site of maximal acceleration or the through-plane velocity encoding slice is not placed perpendicular to the maximal direction of flow.¹⁵⁹

Planimetry of the stenotic orifice area can also be obtained to assess valve area (Fig. 16–40B and C). Compared to ultrasound as the reference standard, CMR has also demonstrated good accuracy in the aortic¹⁶² and mitral¹⁶⁰ positions. Other evolving applications of CMR in aortic stenosis include the detection of localized fibrosis with LGE, which has demonstrated independent prognostic significance,¹⁶³ assessment of diffuse fibrosis with T1 mapping,¹⁶⁴ or planning transcutaneous valve interventions.¹⁶⁵

Valvular Regurgitation

High-resolution cine imaging in one of the long-axis orientations of the left ventricle is helpful to demonstrate leaflet abnormalities such as prolapse, tethering, or systolic anterior motion.² Also using cine images, LV and RV stroke volumes can be calculated and are equal in normal conditions. In the presence of a single regurgitant valve, the difference between these two stroke volumes represents the regurgitant volume; however, this method is not reliable if more than one regurgitant lesion or other abnormalities, such as intracardiac shunts, are present. An alternative method that is used occasionally is direct planimetry of the regurgitant orifice on cine or PC images.^166,167

Today, calculation of the regurgitant volume of blood or flow is more frequently performed using PC, alone or in combination with cine imaging. PC-based approaches for aortic or mitral regurgitation have also been found to be superior to transthoracic echocardiography in terms of reproducibility,¹⁶⁸ and are increasingly used as the reference standard.¹⁶⁹ In semilunar valves, regurgitant volume is measured directly from the diastolic retrograde flow detected with PC in the ascending aorta or main pulmonary artery. The regurgitant fraction is then calculated as the ratio of retrograde volume to total systolic forward volume (see Fig. 16–39B). This approach has been validated in aortic¹⁷⁰ and pulmonary regurgitation,¹⁷¹ and it has high interstudy reproducibility.¹⁷² In the case of atrioventricular valves, flow can similarly be measured at the tricuspid or mitral levels, but this approach is usually considered unreliable.¹⁷³ The most accurate method is the quantification of regurgitant volume as the difference between the stroke volume calculated by volumetric analysis and that obtained with PC of the pulmonary artery or ascending aorta for tricuspid or mitral insufficiency, respectively. This method can be used in the presence of multiple regurgitant lesions. Measurement of mitral regurgitation has been validated against catheterization or Doppler echocardiography.^174,175

From a diagnostic perspective, while echocardiographic thresholds are applied to the quantification of stenosis severity, CMR-specific cutoffs for regurgitation have been derived by optimization with ultrasound¹⁷⁶ (Table 16–4). Contemporary evidence additionally indicates the potential of these approaches to predict outcome and guide therapy. In a prospective, multicenter study of 113 patients with aortic regurgitation,¹⁷⁷ LV end-diastolic volume > 246 mL, regurgitant volume > 42 mL, and regurgitant fraction > 33% were independent predictors of guideline-based need for valvular replacement during a mean follow-up of 2.6 years. Another prospective, multicenter study of 103 patients with mitral regurgitation¹⁷⁸ demonstrated modest agreement between echocardiographic and CMR-derived severity, which was overall higher with ultrasound. However, in the 26 patients with repeated evaluation after valve surgery, CMR regurgitant volume, but not echocardiographic severity, correlated strongly with reverse LV remodeling.

Ventricular assessment with CMR adds meaningful information in the assessment of valvular regurgitation. In the case of mitral insufficiency, quantification of LV end-systolic volume may demonstrate abnormal remodeling even in the presence of normal diameters.¹⁷⁹ Evaluation of LGE can demonstrate the relationships between scar characteristics and valvular dysfunction in ischemic mitral regurgitation.¹⁸⁰ Similarly, in patients with mitral valve prolapse, the presence of LGE in the LV inferobasal segment and papillary muscles has been linked to complex ventricular arrhythmias and possibly sudden death.¹⁸¹ Also, T1-mapping techniques are being used to evaluate diffuse myocardial fibrosis in regurgitant disease.¹⁸²

Noninvasive imaging with CMR or CT is often performed prior to pulmonary vein ablation for AF.^1,144 Currently, these technologies provide a “road map” for positioning catheters along the circumference of the pulmonary vein ostia during the ablation procedure, although the impact of this approach on procedure duration or success remains uncertain.^183,184 Contrast-enhanced MRA is the cornerstone of left atrial mapping with MRI, but it can be replaced and/or complemented with cine imaging, 3D SSFP, or (particularly in the presence of a stenosis) PC. These sequences can provide clinically relevant information regarding not only anatomy but also left atrial function and structural remodeling.

Left Atrial and Pulmonary Vein Angiography

Contrast-enhanced MRA is able to accurately depict the number, location, orientation, and dimensions of the pulmonary veins, demonstrating frequent anatomic variants such as a common left trunk or a right middle vein¹⁸⁵ (Fig. 16–41). Although no longer a frequent complication in the era of antral (rather than ostial) ablation, MRA is also well suited to detect pulmonary vein stenosis.¹⁸⁶ While the spatial resolution of CT angiography is superior, CMR provides comparable anatomic information without exposure to ionizing radiation, and is associated with similar procedural success.¹⁸⁷ Several newer study results suggest that left atrial volume,¹⁸⁸ left atrial sphericity,¹⁸⁹ and pulmonary vein size¹⁹⁰ are features that have been associated with higher recurrence rates of arrhythmia after ablation are obtainable during the same examination used to acquire the pulmonary vein angiographic data.

Other

Left atrial function can be studied using cine images. Reduced passive emptying (likely a reflection of increased ventricular end-diastolic pressure) has also been associated with risk of arrhythmia recurrence.¹⁹¹ Although more commonly done with echocardiography, the evaluation of left atrial strain with cine CMR is feasible and has been validated.¹⁹² Reduced strain has been associated with a prior history of stroke,¹⁹³ and with arrhythmia recurrence after ablation.¹⁹⁴ Beyond its association with AF, reduced left atrial function is also a risk marker for incident HF¹⁹⁵ or for impaired prognosis once HF develops.¹⁹⁶

Regarding left atrial appendage characterization with CMR, increased size has been related to higher stroke prevalence.¹⁹⁷ Four different appendage morphologies have been described and were linked to different thromboembolic risk in one large series of patients referred for ablation,¹⁹⁸ although this association could not be replicated in a subsequent larger study.¹⁹⁹ Detection of left atrial appendage thrombus with CMR appears accurate when compared with transesophageal echocardiography,²⁰⁰ although CMR has not been as extensively validated as CT.

A rapidly evolving field is the study of left atrial structural remodeling through visualization of atrial fibrosis with LGE. This application is more challenging than ventricular LGE because of the thin atrial walls, and these assessments require experienced operators. Yet, with appropriate expertise, the technique is feasible and has good intraobserver and interobserver reproducibility.²⁰¹

In limited histological validation studies, atrial wall LGE correlates with fibrosis.²⁰² The amount of LGE is typically expressed as a percentage of left atrial wall (Utah classification): stage I < 10%, stage II ≥ 10% to 19%, stage III ≥ 20% to 29%, and stage IV ≥ 30%. A recent prospective, multicenter, observational study²⁰³ evaluated the relationship between baseline atrial fibrosis and arrhythmia recurrence in 272 patients referred for ablation. There was a progressive increase in recurrence rates across fibrosis categories, suggesting a potential role of CMR in identifying patients unlikely to benefit from intervention.²⁰⁴ Furthermore, LGE can evaluate completeness of postablation lesions, a factor also associated with arrhythmia-free survival.²⁰⁵ Additionally, more extensive left atrial LGE is associated with reduced atrial function,²⁰⁶ appendage thrombus,²⁰⁷ and prior history of stroke.²⁰⁸

CMR can be considered the best modality for noninvasive characterization of cardiac masses^1,144 and may depict lesions not visualized on echocardiography.^209,210 The exception would be very small and mobile masses, such as vegetations. These may be beyond the spatial resolution of the technique and/or averaged out of the image in segmented acquisitions, and they are usually detected more readily with transthoracic or transesophageal echocardiography. The CMR imaging protocol typically involves a combination of cine, black-blood, first-pass contrast-enhanced imaging, tagging, and LGE imaging.² This provides comprehensive information regarding mass number, location, morphology, chamber invasion, and tissue characterization. The latter combines signal intensity on T1- and T2-weighted images (typically in reference to normal myocardium), presence of perfusion, and fibrosis/necrosis within the mass.

Thrombi

In a study of 361 patients with ischemic cardiomyopathy referred for ventricular reconstruction surgery,²¹¹ CMR as well as transthoracic and transesophageal echocardiography all had high specificity for the identification of thrombi. However, respective sensitivities were 88%, 23%, and 40%, indicating that many thrombi may be missed with echocardiography (even with the use of contrast), particularly if mural and/or small.^209,212 Regarding CMR techniques, LGE is able to detect thrombi that may be missed on cine imaging²¹³ (see Fig. 16–25); thus, when there is concern of potential cardiac thrombi, a contrast-enhanced examination should be considered. Most thrombi are chronic and appear isointense on T1-weighted and iso/hypointense on T2-weighted imaging in comparison with the myocardium. However, subacute thrombi may appear hyperintense on both T1- and T2-weighted imaging (caused by increase in paramagnetic methemoglobin and free water from erythrocyte lysis, respectively).²¹⁴ Clots do not usually perfuse, but some chronic, organized thrombi may develop neovascularization and demonstrate first-pass contrast enhancement and LGE.²¹⁴ In addition, as opposed to tumors, thrombi are typically hyperintense and hypointense with short and long inversion times, respectively (Fig. 16–42).

Tumors

The main strength of CMR in the evaluation of cardiac masses is probably the ability to differentiate between cardiac thrombi and tumors. Features supporting the diagnosis of thrombus include location in the left ventricle adjacent to areas of scar or the left atrial appendage, homogenous appearance, lack of mobility, isointensity or hypointensity on T2-weighted imaging, and absence of perfusion or LGE. Features consistent with tumor include large size, signs of infiltration, hyperintensity on T2-weighted imaging, evidence of perfusion and LGE, and accompanying pericardial or pleural effusions.^210,213,215 However, performing LGE imaging with different inversion times or a “TI-scout” has the best accuracy to distinguish between both entities²¹³ (see Fig. 16–42).

Although less accurate, CMR can also help differentiate benign versus malignant neoplasms. Larger sizes, invasion of adjacent structure(s), presence of pleural or pericardial effusions, prominent perfusion, or positive LGE (Fig. 16–43) are all features seen more commonly in malignancy.^210,213 A few specific characteristics may be helpful in identifying individual tumors.²¹⁴ High signal intensity on T1-weighted images, besides the presence of recent hemorrhage (see above), can also be caused by fat. Together with signal reduction with fat suppression techniques, hyperintensity on T2-weighted imaging, and lack of perfusion/LGE, CMR allows for the straightforward diagnosis of lipoma (Fig. 16–44). Another rare tumor that is typically hyperintense on T1-weighted imaging is metastatic melanoma. Tumors have increased signal intensity on T2-weighted imaging in the presence of high water content, such as in cystic or highly vascular lesions. Pericardial cysts are typically noted in the right cardiophrenic space, are characteristically bright on T2-weighted imaging (Fig. 16–45) because of the proteinaceous fluid contained within, and lack perfusion or LGE. Beyond these examples, the diagnosis of a specific tumor often requires histological confirmation.

Initially, cardiac congenital abnormalities are most frequently identified with transthoracic echocardiography. The role of CMR is typically reserved for cases of complex disease and evaluation of the great vessels or when information derived from ultrasound is insufficient for complete characterization.²¹⁶ CMR is also an attractive modality when serial follow-up is needed after surgical repair of extracardiac structures, particularly in younger individuals.^1,144,217 Comprehensive review of the many different types of congenital malformations of the heart and great vessels or detailed descriptions of specific CMR protocols are beyond the scope of this chapter. The interested reader is referred to other resources^217,218 (see also Chap. 56).

Although dependent on the specific indication, several sequences are commonly used. Breath-hold acquisitions are preferred but may not be possible in infants and young children. General anesthesia may be needed for pediatric examinations when children cannot comply with the examination (typically before age 7 years). Cine imaging is often performed in standard and modified views to obtain measurements of the left ventricle; importantly, RV size and function; and to visualize cardiac valves, shunts, or conduits. A fundamental component is the quantification of Qp/Qs using PC imaging; the most common approach is to measure systemic output at the ascending aorta and pulmonary output at the main pulmonary artery (Fig. 16–46), although other locations can be investigated, such as the inferior and superior vena cavae or the right and left main pulmonary arteries. PC-derived Qp/Qs is superbly accurate and has been extensively validated.^219,220 Other potential applications of PC imaging include evaluation of valvular heart disease, characterization of differential lung perfusion, and quantification of gradients across narrowed vessels or grafts.

For the evaluation of anatomy, a 3D SSFP sequence is often used and can also document anomalous coronary origin.² This sequence can replace or complement contrast-enhanced 3D MRA (see Chap. 22), which is usually performed during breath-holding. Alternatively, time-resolved MRA techniques (see Chap. 22) allow for the dynamic visualization of contrast passage through the CV system.²²¹ Black-blood imaging can be used to evaluate areas with metallic prosthetic materials that typically cause a larger artifact in bright-blood sequences; yet, stents may be better evaluated with CT angiography. Finally, LGE can be performed to demonstrate myocardial scar, and T1 mapping techniques for quantification of diffuse fibrosis are being actively explored.²²²

Simple Systemic-to-Pulmonary Shunts

Intracardiac shunts such as atrial and ventricular septal defects rarely require CMR for evaluation. The exception may be sinus venosus atrial septal defect, which can be more difficult to detect on echocardiography and cause unexplained RV dilatation. The main role of CMR is usually to provide accurate and noninvasive quantification of RV size/function and shunt severity. Ostium secundum septal defects that are amenable to percutaneous intervention can be adequately identified and measured using en face views (Fig. 16–47) and CMR can provide relevant information such as additional communications or anomalous pulmonary veins.²²³ CMR is more useful in the identification of extracardiac shunts. Anomalous pulmonary vein drainage can be easily depicted using MRA and severity of shunt calculated.²²⁴

Predominantly Obstructive Lesions

Tetralogy of Fallot

Tetralogy of Fallot (TOF) is one of the most common indications for CMR in congenital heart disease, particularly after repair. CMR offers accurate determination of RV size and function, severity of pulmonary regurgitation, patency and dimensions of conduits and/or native arteries, and presence and extent of myocardial scar. In patients with corrected tetralogy of Fallot and need for pulmonary valve replacement, single-center data and large prospective registries have shown associations of CMR-based biventricular ejection fraction and RV hypertrophy with major events, whereas data on volumes have been controversial.^225,226 Regional wall motion abnormalities and/or aneurysms, common in the RV outflow tract (Fig. 16–48), also contribute to systolic dysfunction and exercise intolerance.²²⁷ CMR is well suited for serial imaging of RV or LV size and function²²⁸ and can help guide the timing of surgical replacement of the pulmonary valve; RV volumes can be normalized if surgery is performed while RV end-diastolic volume < 160 mL/m² and end-systolic volume < 80 mL/m².²²⁹ PC is used to quantify the severity of pulmonary regurgitation, rule out residual shunts, and detect pulmonary artery end-diastolic forward flow (indicative of restrictive physiology), and it can be performed also in main pulmonary branches to evaluate differential pulmonary regurgitation and/or perfusion.²³⁰ Contrast-enhanced MRA can depict stenosis of the pulmonary artery, its branches, or a ventriculoarterial conduit; aortic root dilatation; or, particularly prior to surgical repair, the presence of systemic-to-pulmonary collaterals or a patent ductus arteriosus. Finally, the presence of LGE is another common finding in the RV outflow tract and has been associated with adverse markers such as RV dilatation and dysfunction, decreased functional class, and arrhythmias.²³¹

Coarctation of the Aorta

The extent and anatomic severity of aortic coarctation can be accurately depicted with black-blood sequences, 3D SSFP or, particularly, contrast-enhanced MRA (Fig. 16–49). The hemodynamic severity of the coarctation can be determined measuring peak velocity and gradient with PC imaging (see Valvular Heart Disease).²³² However, peak gradient may be reduced in the presence of extensive collateral circulation, which can be depicted anatomically with MRA or functionally with PC. The latter is acquired both at the proximal and distal descending aorta. In normal conditions, flow in both locations should be similar or slightly lower distally; however, when there is significant collateral circulation, distal flow actually increases and the difference is proportional to the severity of the coarctation.²³² This index, and particularly the combination of the smallest cross-sectional area on MRA and flow deceleration in the distal aorta, provides the best diagnostic accuracies for the identification of significant stenosis or need for intervention.²³³ Serial imaging after repair is recommended to rule out complications such as restenosis or aneurysms that can be readily identified with CMR.²³⁴

Abnormal Cardiac Connections

Transposition of the Great Arteries

D-loop transposition of the great arteries (TGA) is the most common form and requires surgical correction (Fig. 16–50), and the most important role of CMR is the evaluation of potential postoperative complications. Goals of CMR include evaluation of ventricles, residual shunts, baffles/conduits, ischemia, and fibrosis with a combination of cine imaging, PC, contrast first-pass imaging, 3D SSFP and/or MRA, stress perfusion, and LGE.²³⁴ In the case of atrial switch, the most common late complication is the progressive dilatation and dysfunction of the systemic right ventricle, which can be serially evaluated with CMR. Also, an inadequate RV response to dobutamine stress has been linked to adverse events.²³⁵ LGE in the systemic right ventricle can occur and is associated with systolic dysfunction, arrhythmias, and functional deterioration.²³⁶ In cases of arterial switch, stenoses tend to be most frequent in the RV outflow tract and pulmonary branches, particularly the right one if the pulmonary artery is positioned anterior to the ascending aorta (LeCompte maneuver). Other potential complications include stenoses of ventriculoarterial conduits, dilatation of the neoaortic root, or obstruction of the reimplanted coronary arteries.²³⁷

L-loop or congenitally corrected TGA is less common and does not have abnormal circulation. However, just like in D-loop TGA after atrial switch, the most common late complication is the failure of the systemic (congenitally right) ventricle. As described above, an abnormal response to stress or the presence of LGE may be markers of impaired prognosis.^235,236

Single-Ventricle Physiology

Single-ventricle or univentricular heart physiology may result from a number of complex anomalies, including hypoplastic left heart syndrome. The standard palliative repair is the deviation of systemic flow directly to the lungs (Fontan circulation). CMR is possibly the best available technique today for evaluation of ventricular status and central circulation before and after Fontan.²³⁸ Retrospective and prospective randomized data have shown that CMR can replace invasive catheterization prior to Fontan on many instances, with similar short-term and long-term outcomes.^239,240 The presence and extent of systemic-to-pulmonary collaterals is an important determinant of postoperative course and can be characterized anatomically and functionally both before and after surgery.²⁴¹ CMR can also be used to evaluate the different conduits and anastomosis of the Fontan stages,²⁴² which may occlude or narrow partly because of increased systemic venous pressure and associated blood stasis and thrombosis. Indexed ventricular end-diastolic volume has been associated with transplant-free survival,²⁴³ and the extent of LGE has been linked to ventricular dilatation, hypertrophy, and dysfunction, as well as arrhythmias.²⁴⁴

The use of CMR for pulmonary hypertension (PH) is not advocated in clinical guidelines/recommendations with the exception of PH associated with congenital heart disease.²³⁴ The main role of CMR is the quantitative evaluation of RV performance, although flow imaging of the great arteries, pulmonary MRA, and LGE imaging are also important in disease characterization. One of the potential applications of CMR is the determination of underlying etiology when it is uncertain. Quantification Qp/Qs can identify the presence of an unsuspected shunt (see section on Congenital Heart Disease). MRA has good diagnostic accuracy to detect chronic thromboembolism,²⁴⁵ although CT and, particularly, ventilation/perfusion scintigraphy are typically favored for this application. Other findings can raise suspicion for alternative etiologies.

A number of parameters have demonstrated discriminatory ability to detect the presence of PH. These include, among others, biventricular volumes, function, mass, and geometry (Fig. 16–51); LGE; and pulmonary artery size, stiffness, mean blood velocity, and flow vortices.^{246,247,248,249} However, none of these parameters is considered accurate to justify routine use.²⁵⁰ CMR-based approaches for the quantification of pulmonary hemodynamics have also been developed; the most extensively validated estimates pulmonary vascular resistance using RV ejection fraction and pulmonary artery mean velocity,^251,252 with preliminary data suggesting potential prognostic value.²⁵³ Other CMR indices have been linked to reduced survival and include increased RV volumes and decreased RV ejection fraction or stroke volume.^254,255 CMR can also be used to track serial changes in ventricular volumes and function, assessing the effects of therapy or progressive deterioration, which also portends poor outcomes.^254,256 Finally, reduced pulsatility of the pulmonary artery is similarly associated with increased mortality.²⁵⁷

The authors are grateful to Han W. Kim, Afshin Farzaneh-Far, Igor Klem, Wolfgang Rehwald, and Raymond J. Kim, the authors of this chapter in the 13th edition, for reuse of Figures 16-1 and 16-2.