Multimodality Noninvasive Imaging for Assessment of Congenital Heart Disease

Abstract

HomeCirculation: Cardiovascular ImagingVol. 3, No. 1Multimodality Noninvasive Imaging for Assessment of Congenital Heart Disease Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBMultimodality Noninvasive Imaging for Assessment of Congenital Heart Disease Ashwin Prakash, MD, Andrew J. Powell, MD and Tal Geva, MD Ashwin PrakashAshwin Prakash From the Department of Cardiology, Children’s Hospital Boston, Department of Pediatrics, Harvard Medical School, Boston, Mass. Search for more papers by this author , Andrew J. PowellAndrew J. Powell From the Department of Cardiology, Children’s Hospital Boston, Department of Pediatrics, Harvard Medical School, Boston, Mass. Search for more papers by this author and Tal GevaTal Geva From the Department of Cardiology, Children’s Hospital Boston, Department of Pediatrics, Harvard Medical School, Boston, Mass. Search for more papers by this author Originally published1 Jan 2010https://doi.org/10.1161/CIRCIMAGING.109.875021Circulation: Cardiovascular Imaging. 2010;3:112–125Major advances in the field of pediatric cardiology and cardiac surgery over the last several decades have led to a dramatic improvement in survival rates for most forms of congenital heart disease (CHD). For example, hypoplastic left heart syndrome, a previously lethal defect, now has early survival rates up to 90% at major centers.1 These improved outcomes have produced a growing population of survivors with complex CHD who are now reaching adulthood (Figure 1). During this period, improvements in surgical and medical treatments have been accompanied by developments in diagnostic modalities. Echocardiography has replaced catheterization as the primary diagnostic modality, and it is now uncommon for newborn infants to undergo catheterization for purely diagnostic purposes. Although echocardiography remains the bedrock of noninvasive cardiac imaging, the array of diagnostic modalities and techniques available continue to grow and this has spawned the specialty of “noninvasive cardiac imaging” and the need for the “cardiac imager” to be adept in all the different modalities. Download figureDownload PowerPointFigure 1. Percentage of patients under the age of 1 year (grey bars) and over the age of 18 years (black bars) undergoing echocardiography at Children’s Hospital Boston from 1983 through 2006. Note the reverse trends of these age groups reflecting the steady increase in the proportion of adult patients with congenital heart disease. Although the absolute number of infants undergoing echocardiography during this time period has increased, their proportion has steadily declined.ModalitiesEchocardiography, cardiac magnetic resonance (CMR), and cardiac computed tomography (CCT) are the primary modalities used for noninvasive cardiac imaging in patients with CHD. Nuclear scintigraphy is used in selected circumstances. The Table summarizes the strengths and weaknesses of each modality. Figure 2 shows temporal trends in utilization for the various noninvasive cardiac imaging techniques at our center. It is clear that echocardiography is the most frequently used modality for initial assessment and follow-up of most patients with CHD, with CMR and CCT playing complementary but much smaller roles. Diagnostic cardiac catheterization is used sparingly but continues to be used in selected circumstances where detailed hemodynamic assessment is important. Based on trends at our center, the marked increase in use of noninvasive imaging over the past nearly 3 decades is driven predominantly by a growing population of patients with repaired or palliated heart disease and is not related to increased incidence of CHD or increased frequency of testing in individual patients. Figure 1 shows that a progressively increasing proportion of echocardiograms are now performed on adult survivors of CHD. Table. Comparison of Imaging ModalitiesEchocardiographyCMRCCTNuclear Scintigraphy*From Center for Medicare and Medicaid Services, National Physician Fee Schedule: htp://www.cms.hhs.gov/PFSlookup/03_PFS_Document.asp.†Sum of relative value units for CPT codes 93303, 93325, and 93320.‡CPT code 75562.�CPT code 71275.∥CPT code 78465.�Temporal resolution for nuclear techniques is variable and depends on the radiotracer and counts.**When measurement of ventricular stroke volume differential is physiologically appropriate.Availability+++++++++ ungated; ++ gated+++Portability++++−−−Cost (relative value units)*9.11†22.51‡14.39�13.59∥Radiation risk−−++++++++Artifacts from stainless steel implants+++++−Sedation requirements in young children+++++++++++Spatial resolution<1 mm1–2 mm<1 mm5–10 mmTemporal resolution20 ms30 ms60 ms (gated)−�Intracardiac morphology++++++++++ ungated; ++++ gated−Extracardiac vasculature++++++++++−Ventricular function quantification+++++++− ungated; +++ gated+++Regional function assessment++++++++− ungated; ++ gated+Diastolic function+++++−−Flow quantification+++++−−Quantification of valve regurgitation+++++++− ungated; + gated**−Assessment of pressure gradients+++++−−Tissue characterization+++++++Myocardial viability++++++++++First-pass perfusion++++++−++++Stress imaging+++++++−++++Fetal imaging+++++−−Coronary artery imaging+++++++++−Trachea and main stem bronchi−+++++++−Download figureDownload PowerPointFigure 2. Temporal trends in use of diagnostic modalities and surgery at Children’s Hospital Boston from 1983 through 2008. A, Despite a relatively modest growth in surgery and catheterization, use of echocardiography and CMR has increased steadily. B, Decreased utilization of diagnostic catheterization coupled with a steady increase in transcatheter interventions, modest increase in cardiac surgery, and rapid increase in use of CMR. Cath indicates cardiac catheterization; Echo, echocardiography; Surg, cardiac surgery.ChallengesAn ideal modality used for noninvasive imaging of CHD should be able to delineate all aspects of the anatomy, including abnormalities of cardiac structure as well as those involving extracardiac vessels, evaluate physiological consequences of CHD such as measurement of blood flow and pressure gradients across stenotic valves or blood vessels, be cost-effective and portable, not cause excessive discomfort and morbidity, and not expose patients to harmful effects of ionizing radiation. No single modality satisfies all these requirements because noninvasive imaging of CHD poses several unique challenges. Patients range in size from a 200-g fetus to an adult weighing more than 120 kg. Each extreme poses technical difficulties specific to the imaging modality used. For example, in imaging a fetus or newborn infant, a technique with high spatial resolution such as echocardiography performs well, especially because ultrasound windows are usually good. However, the diagnostic yield of echocardiography is often limited in adults, especially after cardiac operations because of diminished ultrasound windows. CMR and CCT are well suited to adults because acoustic windows do not limit image quality but face significant technical challenges in imaging of a fetus or newborn.EchocardiographySince the 1980s, echocardiography has been the noninvasive imaging modality of choice for diagnosis and follow-up of children and adults with CHD and has been shown to be reliable in the diagnosis of most forms of CHD, with major diagnostic errors occurring in only 0.2% to 2% infants.2,3 New echocardiographic techniques developed in recent years, including real-time 3D echocardiography, strain/strain rate imaging, and speckle tracking, have greatly expanded the capabilities of cardiac ultrasound to evaluate anatomy and physiology of CHD.CMRTechnical advances during the last decade have brought CMR into the mainstream of noninvasive cardiac imaging. Well-established clinical applications of CMR in patients with CHD include anatomic assessment of cardiovascular anomalies before and after surgery, quantification of biventricular function, magnetic resonance angiography (MRA), measurement of systemic and pulmonary blood flow, quantification of valve regurgitation, identification of myocardial ischemia and fibrosis, and tissue characterization.CCTThe role of CCT in evaluating the thoracic vasculature and the tracheo-bronchial tree is now well established.4,5 Recent advances in multidetector technology have led to improved spatial and temporal resolutions allowing coronary artery imaging and gated cine imaging to evaluate ventricular function. CT scanners are also readily available and easy to use compared with CMR. A major disadvantage of CCT, especially in children, is the exposure to ionizing radiation. This drawback is compounded when multiple follow-up studies are necessary.Nuclear ScintigraphyThese techniques use radioisotope-labeled compounds to quantify ventricular function, blood flow, myocardial perfusion, and metabolism.6 Ventricular volumes, ejection fraction, cardiac output, and regurgitant fraction can be calculated using multiple gated acquisitions obtained after equilibration of 99mTc-labeled red blood cells or albumin. Reversible myocardial ischemia can be identified by assessing myocardial perfusion under stress based on uptake of 99mTc or 201Tl measured using single-photon emission computed tomography (Figure 3). Positron emission tomography can be used to evaluate myocardial viability and metabolism. Lung perfusion can be quantified using 99mTc-labeled macroaggregated albumin. This technique is commonly used to determine differential flow to each lung, which can be helpful in determining the physiological significance of pulmonary artery or vein stenosis. However, nuclear scintigraphy plays a limited role in the pediatric age group due to risks associated with exposure to ionizing radiation and its relatively low spatial resolution. Download figureDownload PowerPointFigure 3. Multimodality evaluation of cardiac anatomy, function, and myocardial viability in a 4-year-old child with delayed diagnosis of Kawasaki disease and coronary aneurysms. A, Conventional coronary angiography demonstrated multiple aneurysms in the right coronary artery. The circumflex coronary artery was occluded (not shown). B, Myocardial perfusion imaging by single-photon emission computed tomography demonstrated a fixed perfusion defect in the inferior left ventricular wall (arrow). C, Myocardial delayed enhancement CMR imaging demonstrated transmural late gadolinium enhancement in a corresponding area of the left ventricle consistent with myocardial infarction.Radiation RisksAmong noninvasive modalities for cardiac imaging, CCT and nuclear scintigraphy involve exposure to ionizing radiation. A growing body of literature has shown that exposure to even low doses of ionizing radiation increases the lifetime risk of developing cancer.7 Importantly, children are at much greater risk than adults from a given dose of radiation both because they are inherently more radiosensitive and because they have more remaining years of life during which a radiation-induced cancer could develop. For example, compared with a 40-year-old adult receiving a similar dose of radiation to the chest, an infant has a 4- to 5-fold higher lifetime risk of developing lung cancer.8 In addition, organs receive higher radiation doses when scanned in a child compared with an adult. Radiation dose associated with gated 16-slice CCT (≈15 mSv) is almost 3-fold larger than that associated with conventional coronary angiography (≈5 mSv).9 Several new techniques to reduce radiation dose of CCT are being developed, but their implementation in clinical practice remains limited at the present time.10 In view of these data, young children undergoing CCT seem especially susceptible to radiation risks. In children with complex CHD, this risk may be compounded by their previous or subsequent exposure to ionizing radiation during cardiac catheterization. Although CCT can provide high-quality imaging in patients with CHD, the often underappreciated risks of exposure to ionizing radiation should be considered carefully when choosing the imaging modality for a particular patient. To reduce these risks to “as low as reasonably attainable” levels,11 it seems sensible that CCT be used only when other imaging modalities such as echocardiography or CMR are inconclusive, unavailable, or contraindicated.Radiation doses associated with nuclear scintigraphy are also relatively large. The effective doses associated with a myocardial perfusion scan using 99mTc sestamibi at rest and stress (≈11 mSv) are almost twice those associated with coronary angiography.12 Therefore, when myocardial perfusion imaging is necessary in children, alternative modalities such as echocardiography with exercise or pharmacological stress or CMR with pharmacological stress are preferable.Age-Specific ConsiderationsBecause the challenges relevant to cardiac imaging of CHD are different in a fetus, infant, child, adolescent, or adult, age-specific considerations are worth discussing.FetusWith advances in obstetric ultrasound screening, approximately 30% to 50% of severe CHD is diagnosed before birth.13 Echocardiography is the primary imaging modality used for fetal cardiac imaging, with excellent diagnostic accuracy for most CHD except for atrial or ventricular septal defects, partially anomalous pulmonary venous connection, anomalies of the coronary arteries, and coarctation of the aorta.14 Fetal arrhythmias can also be detected and characterized using M-mode, pulsed Doppler, and tissue Doppler imaging.15 In addition to anatomic evaluation, a wealth of physiological data such as measures of systolic and diastolic ventricular function, cardiac output, and Doppler parameters of fetal well-being can also be obtained.16 Imaging for suspected CHD is typically performed between 18 and 22 weeks of gestation, although successful imaging during the first trimester (11 to 15 weeks) has been reported using both transabdominal and transvaginal approaches.17Fetal MRI is being used increasingly for the evaluation of noncardiac congenital anomalies such as central nervous system abnormalities and congenital diaphragmatic hernia.18 CMR for fetal cardiac imaging has also been recently shown to be feasible.19 Several theoretical advantages make CMR attractive for fetal imaging including the ability to perform tomographic imaging in arbitrary planes independent of acoustic windows. However, significant technical challenges to fetal CMR remain, including limited spatial and temporal resolutions, lack of commercially available methods for fetal cardiac gating, fetal motion during scanning, and paucity of safety data, especially during the first trimester.Infants and Children <8 YearsEchocardiography is the primary cardiac diagnostic modality in this age group, both for establishing initial diagnosis and for follow-up after medical or surgical treatment. Most children in this age group have adequate acoustic windows, and an accurate diagnosis can be established even in patients with the most complex anatomy and in low-birth-weight infants.3 Sedation may be required in infants and young children who are unable to cooperate with the examination.20 Rarely, additional imaging modalities are necessary for anatomic assessment of the extracardiac vasculature, further delineation of spatial orientation or relationship of cardiac chambers or vessels, tissue characterization (Figure 4), or to obtain additional physiological data such as quantification of ventricular size and function and quantification of valve regurgitation. In these instances, other diagnostic techniques such as CMR can be used selectively. The accuracy of CMR in this age group in the evaluation of a wide spectrum of congenital heart defects has been established.21–23 Questions regarding the extracardiac vasculature can also be answered using CCT.24 Its use should be balanced against the risks of ionizing radiation exposure. Download figureDownload PowerPointFigure 4. Echocardiographic and CMR evaluation of a large cardiac tumor in a newborn. A, 2D echocardiography demonstrated a single large mushroom-shaped echogenic mass arising from the ventricular septum. Differential diagnosis included fibroma, rhabdomyoma, and hemangioma. B, CMR was performed for tissue characterization and demonstrated the large solitary homogenous septal tumor with a small pericardial effusion. C, Compared with normal left ventricular myocardium, the tumor was isointense on T1-weighted imaging, hyperintense on T2-weighted imaging, showed poor first pass perfusion, and did not show late gadolinium enhancement. These characteristics supported the diagnosis of rhabdomyoma. D, Histological examination was diagnostic for rhabdomyoma with characteristic “spider cells” (arrowhead). T1 indicates T1-weighted imaging; T2, T2-weighted imaging; Perf, first-pass perfusion imaging; MDE, myocardial delayed enhancement imaging.Adolescents and AdultsTypically, as patients grow larger, there is a progressive degradation in the quality of echocardiographic images due to declining acoustic windows, especially in patients who have undergone prior cardiac surgical procedures. Echocardiography continues to remain the primary diagnostic modality due to its ready availability and ease of use, but CMR plays an increasing role, especially for the evaluation of the extracardiac thoracic vasculature, ventricular function, and flow measurements (Figure 5). CMR is usually preferred over CCT in this age group because it avoids exposure to ionizing radiation and can provide a wealth of functional information. CCT plays an important role in patients with contraindications to CMR, such as pacemaker dependence, or those in whom concomitant evaluation for coronary artery disease is necessary (Figure 6). Download figureDownload PowerPointFigure 5. Noninvasive imaging of postoperative baffle leak in a 20-year-old patient with transitional atrioventricular canal (AVC) and drainage of a left superior vena cava (LSVC) to an unroofed coronary sinus (CS). Surgical repair included AVC repair and baffling of the LSVC to the right atrium (RA). The patient presented 19 years after surgery with unexplained exercise intolerance, hypoxemia (pulse oximetry saturation 91%), and inconclusive echocardiographic evaluation. CMR with velocity-encoded in-plane flow mapping of the LSVC to RA baffle was performed. Blue indicates flow in a superior-to-inferior direction and red indicates flow in the opposite direction. A, Magnitude image in the coronal plane demonstrates a large baffle leak. B, In-plane phase-contrast flow velocity map demonstrates that blood flows from the coronary sinus through the baffle leak into the LA resulting in a right-to-left shunt causing hypoxemia. Ao indicates aorta; LA, left atrium.Download figureDownload PowerPointFigure 6. Use of CCT for assessment of pulmonary venous pathway in an adult patient with transposition of the great arteries after a Mustard operation and pacemaker insertion. Right-sided (RPV) and left-sided (LPV) pulmonary veins drain through an unobstructed pulmonary venous pathway into the right atrium.Imaging AlgorithmEchocardiography is the initial imaging modality used in the evaluation of patients with suspected CHD and should always be performed before other modalities are used. In most patients, echocardiography alone provides sufficient information to complete the diagnostic evaluation. However, in the small proportion of patients in whom echocardiography is incomplete or inconclusive, other diagnostic techniques should be considered, based on the clinical question. A general diagnostic algorithm is presented in Figure 7 and should be tailored to an individual patient’s specific diagnostic questions. Finally, cardiac catheterization still remains the reference standard for angiography and hemodynamic assessment and should be used when data from noninvasive imaging remain incomplete or inconclusive. Download figureDownload PowerPointFigure 7. General diagnostic algorithm for the evaluation of patients with known or suspected CHD. CXR indicates chest x-ray; SPECT, single-photon emission computed tomography; TEE, transesophageal echocardiography.Selected Clinical ApplicationsEvaluation of Ventricular and Myocardial PerformanceSystolic ventricular performance is often a determinant of long-term outcomes in patients with CHD.25 Emerging evidence suggests that diastolic dysfunction may also be an important determinant of outcomes after surgical repair of CHD, and this realization has prompted interest in assessment of diastolic performance using noninvasive techniques.26Ventricular Size and Global Systolic PerformanceEchocardiography is the primary modality used in the assessment of left ventricular (LV) size and function. Due to several technical limitations, M-mode–derived measures have been progressively supplanted by measurements made using 2D techniques, which allow more accurate and reproducible measurements of LV volume, mass, and ejection fraction.27 These methods have been shown to be reasonably accurate in adult patients, but, compared with a reference technique such as CMR, there are several sources of error and considerable interstudy and interobserver variability.28 The accuracy and reproducibility of 2D echocardiographic techniques for assessing LV volume and function have not been studied systematically in infants and children, especially those with CHD. Despite these limitations, data on the range of normal values for ventricular dimensions, volumes, mass, and ejection fraction derived from echocardiography in the pediatric age group are available and are helpful in evaluating the clinical significance of findings.29,30The complex geometry of the right ventricle (RV) makes it difficult to accurately quantify its size and systolic performance. Although several 2D echocardiographic methods have been proposed, none has been shown to be reliable and ranges for normal values are not available.31 With real-time 3D echocardiography, it is possible to quantify ventricular volume and function without the use of geometric assumptions. These techniques have been shown to be accurate and reproducible compared with CMR for quantifying both left and right ventricular volumes and function.32,33 A major limitation of 3D echocardiography is its dependence on adequate acoustic windows, which can be limited after cardiac surgery and in adult patients. Furthermore, unlike 2D echocardiography, ranges for normal values for ventricular volume, mass, and ejection fraction by 3D echocardiography are not available. Expertise in using 3D techniques for routine quantification of LV and RV function is currently limited to a few centers and requires specialized analysis software.To overcome problems associated with complex ventricular geometry, several nongeometric echocardiographic methods that rely on Doppler echocardiography have also been used to assess global ventricular performance. These include the myocardial performance index, dP/dt, systolic annular velocity, and isovolumic acceleration measured using tissue Doppler imaging (TDI).34,35 These parameters have the advantage of being relatively independent of ventricular geometry and less influenced by restricted acoustic windows. Disadvantages include a lack of normal values for children with CHD.CMR is considered the reference techniques for quantifying ventricular volume and global systolic function.36 The technique has been extensively validated against direct measurements in explanted hearts and the results in children are highly reproducible for left and right ventricles, including those with abnormal loading conditions.37 High-quality images can be obtained independent of body size or habitus, which can be especially useful in adolescents and young adults in whom echocardiography is suboptimal. More reproducible measurements are also advantageous in guiding clinical decisions as well as in research trials that rely on longitudinal measures of ventricular size or function.36 Although CMR has the highest accuracy and reproducibility among all noninvasive techniques, it has important limitations. First, CMR in young children usually requires sedation or general anesthesia. Furthermore, only limited normative data are available for young children.38,39 Gated CCT has been shown to be accurate in the quantification of left and right ventricular volumes, mass, and ejection fraction in adults.40,41 CCT is generally not the preferred modality for ventricular function assessment because of its use of ionizing radiation and a relatively low temporal resolution compared with CMR and echocardiography. However, it can be useful in patients with contraindications to CMR.Regional Systolic Ventricular FunctionAlthough regional abnormalities are typically associated with ischemic heart disease, they can also occur in patients with CHD.42 Traditionally, regional function is assessed in a qualitative or semiquantitative fashion, but newer methods for the evaluation of regional abnormalities such as strain and strain rate imaging allow quantitative assessment and have been validated against microsonometry and tagged CMR.43 Age-related changes in LV strain and strain rate in children have been recently described.44 In patients after a Senning operation, Pettersen et al45 showed that contraction pattern of the systemic RV shifts from longitudinal to circumferential shortening and the ventricle does not exhibit normal torsion. Weidemann et al46 used strain rate imaging to demonstrate abnormalities in regional LV and RV function in asymptomatic children after repair of tetralogy of Fallot. Strain imaging has also been shown to be feasible in fetal life.47 Further investigation is needed to determine the clinical utility of strain imaging in children and adults with CHD and the relationship between measurements and clinical outcomes.CMR can also evaluate regional ventricular function. In addition to qualitative and semiquantitative assessment using cine steady-state free precession imaging, tissue-tagged CMR has been validated as an accurate method to assess regional myocardial strain.48 Tagged CMR has been used to show abnormalities in myocardial deformation in children with single ventricle physiology and in patients with a systemic RV.49 Routine clinical use of tagged CMR is hampered by the need for moderately complex image processing and lack of normative values as well as data relating the results with clinical outcomes. A newly described strain-encoded CMR technique may allow more rapid calculation of myocardial strain and strain rates.50Diastolic FunctionDiastolic dysfunction can occur after repair of CHD, and there is some evidence that it may adversely affect outcomes.26 The reference techniques for assessing diastolic performance involve invasive measurements using micromanometer tipped catheters. Various noninvasive measures of diastolic performance have been proposed, but each has important limitations. Current approach to noninvasive assessment of diastolic function incorporates data from atrioventricular valve inflow parameters, pulmonary vein Doppler, and TDI (Figure 8). Age related maturational changes in TDI velocities have been described.51Download figureDownload PowerPointFigure 8. Echocardiographic assessment of LV diastolic function in a 4-year-old child who had undergone transcatheter dilation of valvar aortic stenosis in the newborn period. Reversal of E/A velocity ratio on mitral inflow Doppler is accompanied by prominent reversal of flow in the pulmonary vein during atrial contraction (A wave) and low early diastolic (E′) basal septal velocity on TDI, indicating abnormal diastolic function. As shown in the lowermost panel, speckle tracking of previously acquired 2D images can be used to generate velocity, strain, and strain-rate curves for multiple locations within the myocardium. The utility of these data in assessing diastolic function is under investigation.A few clinical applications of TDI have been reported in the pediatric age group. In children with hypertrophic cardiomyopathy, lower E/E′ ratio has been shown to be associated with an increased risk of adverse clinical outcomes.52 TDI velocities are often abnormally low after cardiac transplantation53 and have been shown to be associated with the risk of graft failure.54Several reports have investigated the use of CMR for the evaluation of diastolic function. Phase contrast techniques can be used to evaluate inflow as well as myocardial tissue velocities.55 In addition, early and late diastolic myocardial strain and strain rate can be calculated using either tissue tagging techniques or the recently reported strain-encoded CMR.56 Although tissue-tagged CMR has been available for more than 2 decades,57 clinical applications remain limited. Fogel et al58 used tagged CMR to study diastolic biomechanics in normal infants and showed that circumferential lengthening strain was highest at the lateral LV wall and that rotational strain was most pronounced at the LV apex.Although several noninvasive tools for assessing diastolic function are available and some have been found to improve diagnosis and risk stratification in adults with diastolic heart failure, their routine clinical use in patients with CHD remains limited. Most of these indices are sensitive to alterations in preload, afterload, and heart rate, all of which can be abnormal in patients with CHD, making interpretation of findings difficult.59 Further, the prognostic value of these indices in patients with CHD awaits further studies.Evaluation of the Functionally Single VentricleAnatomic malformations that result in a functionally single ventricle represent some of the mos