Cardiovascular magnetic resonance in patients with ...

Cardiovascular magnetic resonance in patients with corrected tetralogy of Fallot

Cardiovascular magnetic resonance in patients with corrected tetralogy of Fallot Generous support by Medtronic for the publication of this thesis is gratefully acknowledged. © 2006 by T. Oosterhof, Amsterdam ISBN: 90-9021169-1 The printing of this thesis was financially supported by: Astellas, Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, Farmasel, GE Medical, Guidant, Medis, Merck Sharp & Dohme, Novartis, Orbus, Pfizer, Servier Nederland Farma B.V., Jurriaanse stichting, Interuniversity Cardiology Institute the Netherlands (ICIN), Siemens. Cover and Lay-out: Chris Bor, Medische Fotografie en Illustratie, AMC, Amsterdam, picture on cover by M.A. van Oeveren

Cardiovascular magnetic resonance in patients with corrected tetralogy of Fallot ACADEMISCH PROEFSCHRIFT

ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus prof. mr. P.F. van der Heijden ten overstaan van een door het college voor promoties ingestelde commissie, in het openbaar te verdedigen in de Aula der Universiteit op dinsdag 21 november 2006, te 10.00 uur

door

Thomas Oosterhof

Geboren te Amsterdam

Promotiecommissie Promotor

Prof. dr. B.J.M. Mulder

Co-promotoren

Dr. H.W. Vliegen Prof. dr. A. de Roos

Overige Leden

Prof. dr. J.J. Piek Prof. dr. K.I. Lie, Prof. dr. A.H. Zwinderman Prof. dr. W.A. Helbing Prof. dr. M.G. Hazekamp Prof. dr. A.C. van Rossum

Faculteit der Geneeskunde

Financial support by the Netherlands Heart Foundation for the publication of this thesis is gratefully acknowledged.

Get’em Dan! -Randy Newman -

Aan mijn ouders, aan Maartje

TABLE OF CONTENTS Chapter 1 Introduction and outline of the thesis Am Heart J 2006;151:265-272

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Chapter 2 Disparity between dobutamine stress and physical exercise magnetic resonance imaging in patients with an intra-atrial correction for transposition of the great arteries. J Cardiovasc Magn Reson 2005;7:383-9

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Chapter 3 Comparison of segmental and global systemic ventricular function at rest and during dobutamine stress between patients with transposition and congenitally corrected transposition. Cardiol Young 2005;15:148-53

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Chapter 4 Applicability of cardiovascular magnetic resonance: Two case reports Case 1 Cardiovascular magnetic resonance in a pregnant patient with absent pulmonary valve syndrome Int J Cardiovasc Imaging, accepted for publication Case 2 Survival into 7th decade after a Potts palliation for tetralogy of Fallot Congenit Heart Dis, accepted for publication

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Chapter 5 Corrected tetralogy of Fallot: delayed enhancement in right ventricular outflow tract. Radiology 2005;237:868-871

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Chapter 6 Comparison of aortic stiffness in patients with dilated ascending aorta and congenital heart disease with --vs-- without Marfan syndrome Adapted from: Am J Cardiol 2005;95:75-77

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Chapter 7 Optimal timing of pulmonary valve replacement in patients with corrected tetralogy of Fallot Submitted

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Chapter 8 Time course of right ventricular function in repaired tetralogy of Fallot patients Submitted

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Chapter 9 Effects of volume and/or pressure overload secondary to congenital heart disease (Tetralogy of Fallot or Pulmonary Stenosis) on right ventricular function using cardiovascular magnetic resonance and B-type natriuretic peptide levels. Am J of Cardiol 2006;97:1051-1055

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Chapter 10 Long-term follow-up of homograft function after pulmonary valve replacement in patients with tetralogy of Fallot. Eur Heart J 2006;27:1478-1484

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Chapter 11 Long-term effect of pulmonary valve replacement on QRS duration in patients with corrected tetralogy of Fallot. Heart, accepted for publication

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Chapter 12 Summary

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Summary (Dutch)

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Acknowledgements (Dutch)

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Curriculum Vitae

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C h a p t e r

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Cardiovascular magnetic resonance in the follow up of patients with corrected tetralogy of Fallot: a review

Thomas Oosterhof Barbara J.M. Mulder Hubert W. Vliegen Albert de Roos

Am Heart J 2006;151:265-272

ABSTRACT Cardiovascular Magnetic Resonance (CMR) is becoming an important tool in the clinical management of patients with congenital heart disease. Due to the diverse problems patients may face after initial correction for tetralogy of Fallot and the large amount of CMR techniques that can be applied, creating a patient-orientated imaging protocol is a difficult issue. While it is still not certain what the impact of some parameters, provided by CMR, should be on clinical decision making, new techniques are being developed and applied. In this report we review the current clinical issues in patients with tetralogy of Fallot and review the current implication and limitations of CMR in this patient category.

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Chapter 1

CMR in tetralogy of Fallot

BACKGROUND Of all patients with cyanotic congenital heart disease, Tetralogy of Fallot (TOF) is the most common type malformation, with an estimated incidence of 5% to 6% of all patients with congenital heart disease (1). Total correction for TOF has been available for 40-50 years, with a favorable outcome in most patients (2). Despite the good long-term prognosis, life expectancy is still less than that of the normal age-matched population (3). Today we are faced with an increasing number of adult patients who require regular follow up for complications after initial correction of TOF. These complications mostly consist of pulmonary regurgitation, residual or recurrent pulmonary stenosis, ventricular septal defect (VSD) or right ventricular outflow tract (RVOT) aneurysm. Echocardiography provides information on the presence of right ventricular (RV) dilatation and / or hypertrophy, the presence of tricuspid or pulmonary valvular regurgitation and by Doppler estimation of RV systolic pressure. However, because of well-known limitations, transthoracic echocardiography often fails to provide necessary hemodynamic or anatomic information. Additional anatomic information can be provided by computed tomography (CT), owing to the high spatial resolution (4). Especially for patients, in whom anatomic findings are unclear CT may be a helpful tool. Besides obtaining anatomic images in every plane of choice, cardiovascular magnetic resonance (CMR) gives the opportunity to assess ventricular volumes and/or function, and allows for quantification of flow across all heart valves and large vessels. For serial assessment of RV function CMR is a reliable tool (5). The purpose of this article is to review the role of CMR in the evaluation of patients after correction of TOF and to review its current application and limitations in patient management.

CLINICAL ISSUES Pulmonary regurgitation Pulmonary regurgitation is a common finding after initial correction of TOF. The usage of a patch for relief of right ventricular outflow obstruction during initial repair leads to more pulmonary regurgitation and right ventricular dysfunction compared to a correction without the usage of a patch (infundibulectomy + valvulotomy) (6) However, controversy remains whether a transannular patch may cause more ventricular dysfunction than a patch that is confined to the RV (6, 7). Pulmonary regurgitation may be tolerated for many years without the occurrence of symptoms of RV failure. Therefore a conservative approach was advocated. However, chronic pulmonary regurgitation may eventually lead to severe RV dilatation, impaired ventricular function and an increased risk for ventricular arrhythmias (8-10). Pulmonary valve replacement (PVR) is considered to resolve pulmonary regurgitation and improve cardiac hemodynamics, if it is not planned “too late” (11, 12). In a recent report, it was observed that PVR may lead to normalization of RV volume when it is performed before the RV end-diastolic volume reaches 170 ml/m2 or RV end-systolic volume reaches 85 ml/m2 (13). However, timing of PVR remains controversial, as the favorable hemodynamic effects of PVR have to be weighed against the risk of repeated reoperations for homograft failure.

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Pulmonary stenosis Another hemodynamic problem after initial repair remains subvalvular, valvular or supravalvular stenosis (2, 3). The RV is subjected to chronic elevated pressures and RV hypertrophy develops as an adaptive mechanism. However an inverse relation between RV mass and ejection fraction has been observed, implying that at the long run RV contractility is adversely affected by hypertrophy (7). Possible underlying mechanisms for the inverse relation between RV mass and ejection fraction include demand ischemia, accompanying fibrosis altered ventricular geometry and / or affected electromechanical coupling. Furthermore, in the presence of pulmonary regurgitation pulmonary stenosis seems to aggravate right ventricular dysfunction (14, 15). Valvular or peripheral pulmonary stenosis can be treated non-surgically by angiographic balloon dilatation and stent employment for the latter.

Right ventricular function

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An important determinant for long-term prognosis after correction for TOF is RV function (16-18). RV function after repair may be hampered by the combined effects of pre-operative cyanosis and hypertrophy, operative factors and residual postoperative factors such as pulmonary regurgitation and/or stenosis, as mentioned above (7, 8, 19-21). Furthermore, right ventricular outflow tract aneurysms, usually caused by ventricular outflow tract reconstruction during initial repair, have a negative impact on RV function (7). Although a restrictive right ventricular physiology predicts a slower postoperative recovery after initial repair (22). in the long-term outcome it is associated with a superior exercise performance (23-25). less ventricular dilatation and fewer arrhythmias (26). However some reports could not confirm these findings (25) and the prognostic significance of this factor for long-term follow-up is unknown.

Left ventricular function Left ventricular (LV) function has been identified as an independent predictor of adverse long-term prognosis in patients with TOF (27) LV function may be limited as a result of either adverse right to left ventricular interaction mainly through the interventricular septum in a pressure or volume overloaded RV or damage due to delayed initial repair (using arterial shunts) or pre- and per-operative hypoxia (7). In a recent study by Geva et al. (28), it was shown that moderate or severe LV systolic dysfunction is independently associated with impaired clinical status after TOF correction.

Sudden cardiac death Sudden death, attributed to sustained ventricular arrhythmias, occurs in as many as 6% of patients after TOF repair (2). A QRS duration ≥ 180 msec has been identified as a marker for the development of malignant ventricular arrhythmias (26). Surgical scars due to ventriculotomy or VSD-patch form the arrhythmia substrate, whereas RV dilatation is thought to trigger ventricular tachycardia. The influence of pulmonary regurgitation on late sudden death has been established by Gatzoulis et al. (10), which suggests a mechanoelectrical interaction. In a report by Helbing et al. (29), the mechanoelectrical interaction is confirmed as QRS duration is influenced by both RV and LV volumes and RV wall mass. Surgical correction

Chapter 1


of pulmonary regurgitation may reduce QRS-duration, accompanied with a reduction in RV end-diastolic volume (30), and is associated with a reduction of arrhythmias (31). In patients with ventricular tachycardia, percutaneously or concomitant intraoperative ablative procedures of the ventricular tachycardial pathway (31) or implantation of an automated intracardiac defibrillator should be performed when appropriate.

Supraventricular tachycardia Supraventricular tachycardia arises in about a third of adults with a corrected TOF and contributes to late morbidity and even mortality (32). For atrial reentrant tachycardia, radiofrequency ablation now yields better results than before and should be performed percutaneously or intra-operatively at the time of surgical repair of underlying hemodynamic lesions (31, 33).

Aortic root dilatation Aortic root dilatation is known to be a feature associated with TOF. Niwa et al. reported that aortic root dilatation probably relates to previous long-standing volume overload (34). An aneurysmatic aortic root may necessitate aortic root replacement (35). However, the timing of surgery (aortic root replacement) for prevention of aortic dissection, remains a controversy (36).

CMR SCANNING General considerations For CMR, an MR scanner with dedicated cardiac software is required, preferably with the latest imaging techniques. Furthermore, supervising physicians and performing technologists should be trained and be experienced with cardiac MR sequences. Especially, in the field of congenital cardiology, knowledge of and experience with the numerous cardiac abnormalities is mandatory. Preferably, a close collaboration between radiologists and cardiologists should be present. CMR normally is tolerated well by patients despite the relatively long scan duration (60 minutes). Contraindications for CMR include presence of serious claustrophobia, pacemaker, or internal cardiac defibrillators. Children should be old enough to follow breath-hold instructions (approximately 7 years and older) or else need to be scanned under (general) anesthesia. Interobserver agreement and interstudy reproducibility for serial assessment of RV volume and function is considered good with cine CMR (5, 37).

Imaging protocol The timing of a typical protocol is listed in table 1. After obtaining scout images and a reference scan, an axial stack of black blood turbo spin echo images is acquired to outline cardiac and non-cardiac anatomy (figure 1). For analysis of valvular and ventricular function we follow the axis of the heart rather than the body axis. Two and four chamber cines (steady state free precession sequences) are acquired for visualization of valvular insufficiency (figure 2). To quantify left and right ventricular function (figure 3), multiple cines are obtained in

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Table 1. CMR scan protocol Image nr. Image Type 1. 2. 3.

Scout images single phase SSFP parallel imaging reference scan Axial black blood TSE Planning scan 4 4. Two-chamber multiphase SSFP Planning scan 5 5. Four chamber multiphase SSFP Planning scan 6 6. RVOT cine multiphase SSFP Planning scan 7 6. Multislice, multiphase axial SSFP Planning scan 8-11 7. Timing MRA 8. MRA pulmonary artery 9. Flow mapping pulmonary trunk 11. Flow mapping tricuspid valve 12. Flow mapping aortic valve 13. Delayed enhancement Total scan duration (min)

Scan duration (min) 0-1 1-5i 5-20 21-22 22-24 24-25 23-24 24-25 25-27 27-28 28-33 33-35 36-38 38-40 40-43 46-49 49-52 52-60 60

Some scans can be omitted according to clinical indication for CMR (i.e. scan 12 when there is no evidence for a VSD (to calculate shunting) or aortic regurgitation. MRA = magnetic resonance angiography, SSFP = steady state free precession, TSE = turbo spin echo.

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Figure 1 In this figure a 3D reconstruction is shown. It is created from the endo- and epicardial contours, which were drawn for calculation of ventricular volumes and function from the multiple short-axis cines (figure 2). This process takes normally about 15 minutes. Note the dilated right ventricle.

the short-axis orientation (figure 2), When cardiac anatomy is complex, we tend to use a transversal stack of cine’s to calculate ventricular function and from these images additional oblique images can be acquired to analyze the anatomy or function (38). An additional cine is aligned along the RVOT to visualize pulmonary insufficiency and right ventricular outflow tract enlargement (7). A contrast enhanced magnetic resonance angiography (MRA) is used to visualize the pulmonary tree (figure 4). To identify the arrival time of Gadolinium in the

Chapter 1


pulmonary artery, a 2D fast gradient-echo or a real time sequence with a high temporal resolution, can be used in combination with a test bolus of 2 ml Gadolinium. The MRA is performed during breath-hold after the estimated arrival time from the previous scan. From the additional RVOT cine and a transversal black blood image, a velocity map across the pulmonary artery is acquired for calculation of pulmonary regurgitant volume (figure 5). A velocity map of the tricuspid valve and the aorta are obtained for diastolic function of the RV and aortic regurgitant volume, respectively. Finally, after identifying the correction inversion time, a delayed enhancement sequence is started 15 minutes after the injection of Gadolinium for the MRA, to analyze fibrosis / scarring in the right / left ventricles (figure 6).

Figure 2 Axial orientated black blood images show the abnormal anatomy of a patient with a pulmonary homograft after initial correction for TOF. Note the right ventricular hypertrophy due to pulmonary stenosis. In the second image a large right ventricular outflow tract can be observed (closed arrow). Ao = Aorta, LA = left atrium, LV = left ventricle, RA = right atrium, RV = right ventricle, RVOT = RV outflow tract.

Figure 3 This figure shows cine still-frame images of a two, a four chamber, and a short axis image. A sort axis image can be obtained from the two and four chamber views, perpendicular to the longaxis of the left ventricle. Note the severely dilated right ventricle in the four chamber view and the RVOT dilatation in the short axis image. Multiple short-axis cines from the apex to the base of the heart (or orientated axial) are used to quantify right and left ventricular function.

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Figure 4 Magnetic resonance angiography (MRA) from volume rendered images of a patient with corrected TOF. Note the stenotic right pulmonary artery (closed arrow) and an aneurysmatic right ventricular outflow tract (open arrow). In the left pulmonary artery no residual stenosis can be observed. MPA = main pulmonary, RPA = right pulmonary artery, LPA = left pulmonary artery, RA = right atrium, RV = right ventricle.

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Figure 5 This figure shows a magnitude and phase image, acquired with velocity mapping of the pulmonary trunk. The flow profile can be created by outlining the pulmonary artery in all phases of a heart cycle. In the graph, pulmonary regurgitation and late diastolic forward flow are clearly shown.

Chapter 1

CMR in tetralogy of Fallot Figure 6 This figure shows delayed enhancement images of the right ventricle. Right ventricular scarring can be observed beginning in the right ventricular outflow tract probably as a result of right ventricular or transannular patching during initial repair. Delayed enhancement is also observed in the posterior alignment of the right ventricle to the left ventricle (A).

INFORMATION PROVIDED BY CMR Pulmonary regurgitation and stenosis With CMR velocity mapping quantification of pulmonary flow allows for accurate calculation of pulmonary regurgitant volume (9, 39, 40) (figure 5), which is not possible with Doppler echocardiography. Flow curves are obtained for flow across the pulmonary valve and from these flow curves pulmonary regurgitant volume and fraction (as percentage from pulmonary forward flow) are calculated (Figure 4). Furthermore, with velocity mapping maximal velocity across the pulmonary valve can be calculated in the presence of pulmonary stenosis.

RV size and function Firstly, for qualitative or simple quantitative analysis of RV size and ejection fraction, transthoracic 2-D echocardiography methods can be used in the follow up after repair for TOF. Furthermore, eochocardiography may provide relatively load-independent markers of RV systolic function as well (41). However, for exact measurement of right ventricular volumes and ejection fraction CMR is the most accurate imaging modality (16, 42-45). Furthermore, CMR may give a unrestricted view of the right ventricular outflow tract and an aneurysmatic enlargement can be observed (Figures 3 and 4) (7) .The end-diastolic volume (EDV) and end-systolic volume (ESV) are calculated by manually drawing endocardial contours at enddiastole and end-systole respectively on cine loops, oriented axial or along the short axis of the left ventricle (figure 2). Ejection fraction (EF) is calculated by dividing stroke volume (EDV minus ESV) by EDV. Correction of EF for regurgitant volume can be achieved by dividing the net pulmonary forward flow (acquired with velocity mapping of the pulmonary trunk) by EDV (11, 46) This method provides for a correction of (the overestimation of) ventricular function in the presence of pulmonary regurgitation due to the backflow of a (large) part of the stroke volume during diastole. This parameter is of additional value in the assessment of RV function in patients with moderate to severe (pulmonary) valvular regurgitation (11, 46).

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Peripheral Pulmonary stenosis Peripheral pulmonary stenosis is commonly associated with TOF and can be observed with MRA. This technique is a noninvasive alternative to cardiac catheterization with x-ray angiography and allows for calculations of the caliber of the pulmonary arteries (47). In our institution, in every TOF patient undergoing CMR the pulmonary arteries are visualized at least once, due to the limitations with echocardiography to visualize the pulmonary arteries. Difference in flow between the stenotic and non-stenotic vessel, acquired with velocity mapping of both pulmonary arteries, may give additional information on the severity of stenosis.

Scarring of the ventricles Delayed enhancement can identify scarring / fibrosis of the ventricles, also in patients without ischemic heart disease (48). In a recent report from our institution, with delayed enhancement imaging scarring of the right ventricular outflow tract with concurrent dilatation was observed (figure 6), mostly likely due to the initial surgery (49). Possibly, these scars may contribute to arrhythmia propensity or aneurysm formation of the right ventricular outflow tract.

Additional information 18

In the presence of a VSD, the amount of left-to-right shunting can be calculated with velocity mapping of the pulmonary artery and the aorta (50). Aortic root diameters and aortic insufficiency can be quantified with an additional velocity mapping of the aortic valve (51). With velocity mapping of the tricuspid valve, right ventricular diastolic function (restrictive physiology) can be assessed by calculating E/A ratio and deceleration time (25, 52).

WHEN TO PRESCRIBE CMR? Currently, CMR is considered in all TOF patients years after initial correction. Further follow-up CMR is performed when residual lesions are present or when the clinical status of the patient deteriorates (decrease in validity or exercise capacity, presence of arrhythmias, etc.). All patients who require CMR will receive a MRA of the pulmonary artery at least once to visualize the pulmonary tree. CMR has proven it’s usefulness by providing parameters that are more accurate and reproducible than conventional techniques. Although, it is unclear how CMR is incorporated, exactly, into clinical decision-making, more reports, in which CMR is used for this purpose, are to be expected. We recommend that all TOF patients should undergo, at least once, anatomic and functional evaluation with CMR and, when significant residual lesions are present, follow-up CMR every 1 – 5 years, depending on clinical status and CMR findings. A question of debate remains the optimal timing of PVR in patients with corrected TOF. Vliegen et al. (11) reported which CMR parameters can be used for selection of patients for PVR: severe RV dilatation (RV-EDV > 150 ml/m2 or > twice LV-EDV) with moderate (>20% and 40%) pulmonary regurgitation. Recently, Therrien et al. have shown that

Chapter 1


when RV end-diastolic volume exceeds 170 ml/m2 or RV end-systolic volume exceeds 85 ml/ m2, RV volumes do not decrease to normal values after surgery (13). However, the beneficial hemodynamic effects of PVR still have to be weighed against the need for reoperation for homograft failure and further studies are needed to clarify these initial results. Further co-indications for PVR may include presence of (supra)-ventricular tachycardia, tricuspid regurgitation, (peripheral) pulmonary stenosis, prolonged QRS duration (QRS > 180 ms) or residual ventricular septal defect. In patients, who did undergo pulmonary valve replacement, serial follow-up with magnetic resonance can be of clinical use. Firstly it has been shown recently that the presence of pulmonary regurgitation post-operatively negatively affects improvement of RV function.44 Secondly, the presence of possible homograft obstruction (proximal to the valve, valvular or distal to the valve) can easily be sought with the techniques described above.

FUTURE PERSPECTIVES Exercise studies, apart from their fundamental relevance to understanding various physiological adaptation mechanisms in health and in disease, may provide objective parameters in the clinical evaluation of patients with congenital heart disease. Evaluation of cardiac function during stress (physical or pharmacologic) allows us to detect ventricular dysfunction which may not be present at rest (decreased cardiac reserve) (14, 53). However, clinical implementation of the provided parameters needs to be evaluated. A segmented inversion recovery ultra fast gradient echo sequence has been proven to be effective in identifying the presence and extent of acute and chronic infarcted tissue in the myocardium (54). In patients with non-ischemic heart disease different patterns of delayed enhancement have been observed as well (48, 55). Scarring has been observed in the right ventricle of patients after correction for TOF (figure 6), most likely as a result of initial repair (49). The clinical and prognostic significance of delayed enhancement in these patients is currently unknown. These surgery-related scars may contribute to the development of ventricular tachycardias (49). Finally, the recent implementation of fast (cine) CMR imaging along with the inherent ability of CMR to create images in any orthogonal plane makes it attractive for guiding interventional procedures. Kuehne et al. (56) have shown that stent deployment in the pulmonary position is feasible with MR imaging guiding with possible post-interventional assessment of stent morphology and blood flow through the stent. Razavi et al. (57) reported that MR guided cardiac catheterization is safe and practical in a clinical setting, allows better soft tissue visualization, provides more pertinent physiological information, and results in lower radiation exposure than do conventional X-ray guided techniques. MR guidance could become the method of choice for diagnostic cardiac catheterization.

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CONCLUSION In this report we have identified the additional role CMR may play in the clinical evaluation of patients with corrected TOF. Quantification of the amount of pulmonary regurgitant volume and of the consequent biventricular dysfunction with CMR allows for a more accurate selection of patients who may benefit from surgical treatment. Secondly, by visualizing the pulmonary artery in great detail with MRA patients may obviate (invasive) x-ray angiography. However the exact implementation of CMR in patient management and the therapeutic consequences of the provided parameters need to be evaluated in large follow-up studies. While the incorporation into clinical practice slowly takes place new CMR techniques are being developed aiding patient management, such as cardiac catheterization guided by CMR.

OUTLINE OF THE THESIS

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In chapter 2, CMR is used to compare the hemodynamic response to dobutamine stress with the response to physical exercise. Thirty-nine patients with chronic, systemic RV pressure overload and 25 controls are studied with dobutamine stress CMR or physical exercise CMR. Chapter 3 describes the differences between two groups of patients with chronic, systemic RV pressure overload. We compare segmental RV function at rest and during dobutamine stress in these patients. Chapter 4 comprises two case reports. In the first report, we discuss the CMR techniques that should and should preferably not be used during pregnancy. In the second case report, we describe how magnetic resonance angiography is used to verify if a surgically created aorta-pulmonary shunt was patent. In chapter 5, the presence of fibrosis was evaluated in 24 adult patients with corrected tetralogy of Fallot using delayed enhancement CMR. The presence of fibrosis was related to initial surgical correction and morphology of the right ventricular outflow tract. In chapter 6, we analyzed aortic stiffness in patients with dilated ascending aorta and congenital heart disease. We compared aortic stiffness in patients with versus those without Marfan’s syndrome. In chapter 7, optimal timing of pulmonary valve replacement is assessed by comparing pre- and postoperative CMR examinations in 71 patients with corrected tetralogy of Fallot. We analyze whether a point of no return exists and if pre-operative cut-off values can be identified for normalization of RV volumes after surgery. Chapter 8 describes the natural course of RV volumes and function over time in patients with corrected tetralogy of Fallot. We analyze differences in the course of RV function between patients with various forms of initial correction during childhood. In chapter 9, we analyze the effects of RV pressure and/or RV volume overload on right ventricular function and cardiac neurohormone (brain natriuretic peptide) levels. The results are presented on the use of brain natriuretic peptide as a marker for RV dysfunction. In chapter 10 the long-term outcomes of pulmonary valve replacement in 158 patients with corrected tetralogy of Fallot are described. In chapter 11 we analyze the effect of pulmonary valve replacement on QRS duration. In 99 patients we

Chapter 1


present the long-term course of QRS duration after surgery. In chapter 12, a short summary is given of the thesis.

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Chapter 1


30. van Huysduynen BH, van Straten A, Swenne CA, Maan AC, van Eck HJ, Schalij MJ, van der Wall EE, de Roos A, Hazekamp MG, Vliegen HW. Reduction of QRS duration after pulmonary valve replacement in adult Fallot patients is related to reduction of right ventricular volume. Eur Heart J 2005. 31. Therrien J, Siu SC, Harris L, Dore A, Niwa K, Janousek J, Williams WG, Webb G, Gatzoulis MA. Impact of pulmonary valve replacement on arrhythmia propensity late after repair of tetralogy of Fallot. Circulation 2001;103:2489-2494. 32. Roos-Hesselink J, Perlroth MG, McGhie J, Spitaels S. Atrial arrhythmias in adults after repair of tetralogy of Fallot. Correlations with clinical, exercise, and echocardiographic findings. Circulation 1995;91:2214-2219. 33. Kopf GS, Mello DM, Kenney KM, Moltedo J, Rollinson NR, Snyder CS. Intraoperative radiofrequency ablation of the atrium: effectiveness for treatment of supraventricular tachycardia in congenital heart surgery. Ann Thorac Surg 2002;74:797-804; discussion 804. 34. Niwa K, Siu SC, Webb GD, Gatzoulis MA. Progressive aortic root dilatation in adults late after repair of tetralogy of Fallot. Circulation 2002;106:1374-1378. 35. Dodds GA, 3rd, Warnes CA, Danielson GK. Aortic valve replacement after repair of pulmonary atresia and ventricular septal defect or tetralogy of Fallot. J Thorac Cardiovasc Surg 1997;113:736-741. 36. Oosterhof T, Nollen GJ, van der Wall EE, Spijkerboer A, Hrudova J, Bouma BJ, Dijkgraaf MG, Mulder BJ. Comparison of aortic stiffness in patients with juvenile forms of ascending aortic dilation with --vs--without the marfan syndrome. Am J Cardiol 2005;95:75-77. 37. Alfakih K, Plein S, Thiele H, Jones T, Ridgway JP, Sivananthan MU. Normal human left and right ventricular dimensions for MRI as assessed by turbo gradient echo and steady-state free precession imaging sequences. J Magn Reson Imaging 2003;17:323-329. 38. Alfakih K, Plein S, Bloomer T, Jones T, Ridgway J, Sivananthan M. Comparison of right ventricular volume measurements between axial and short axis orientation using steady-state free precession magnetic resonance imaging. J Magn Reson Imaging 2003;18:25-32. 39. Meier D, Maier S, Bosiger P. Quantitative flow measurements on phantoms and on blood vessels with MR. Magn Reson Med 1988;8:25-34. 40. Rebergen SA, van der Wall EE, Doornbos J, de Roos A. Magnetic resonance measurement of velocity and flow: technique, validation, and cardiovascular applications. Am Heart J 1993;126:1439-1456. 41. Frigiola A, Redington AN, Cullen S, Vogel M. Pulmonary regurgitation is an important determinant of right ventricular contractile dysfunction in patients with surgically repaired tetralogy of Fallot. Circulation 2004;110:II153-157. 42. Pattynama PM, Lamb HJ, Van der Velde EA, Van der Geest RJ, Van der Wall EE, De Roos A. Reproducibility of MRI-derived measurements of right ventricular volumes and myocardial mass. Magn Reson Imaging 1995;13:53-63. 43. Rebergen SA, Niezen RA, Helbing WA, van der Wall EE, de Roos A. Cine gradient-echo MR imaging and MR velocity mapping in the evaluation of congenital heart disease. Radiographics 1996;16:467-481. 44. Helbing WA, de Roos A. Clinical applications of cardiac magnetic resonance imaging after repair of tetralogy of Fallot. Pediatr Cardiol 2000;21:70-79. 45. Niwa K, Uchishiba M, Aotsuka H, Tobita K, Matsuo K, Fujiwara T, Tateno S, Hamada H. Measurement of ventricular volumes by cine magnetic resonance imaging in complex congenital heart disease with morphologically abnormal ventricles. Am Heart J 1996;131:567-575. 46. van Straten A, Vliegen HW, Hazekamp MG, Bax JJ, Schoof PH, Ottenkamp J, van der Wall EE, de Roos A. Right ventricular function after pulmonary valve replacement in patients with tetralogy of Fallot. Radiology 2004;233:824-829.

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47. Geva T, Greil GF, Marshall AC, Landzberg M, Powell AJ. Gadolinium-Enhanced 3-Dimensional Magnetic Resonance Angiography of Pulmonary Blood Supply in Patients With Complex Pulmonary Stenosis or Atresia: Comparison With X-Ray Angiography. Circulation 2002;106:473-478. 48. Tandri H, Saranathan M, Rodriguez ER, Martinez C, Bomma C, Nasir K, Rosen B, Lima JAC, Calkins H, Bluemke DA. Noninvasive detection of myocardial fibrosis in arrhythmogenic right ventricular cardiomyopathy using delayed-enhancement magnetic resonance imaging. Journal of the American College of Cardiology 2005;45:98-103. 49. Oosterhof T, Mulder BJM, Vliegen HW, de Roos A. Late Gadolinium enhancement in patients with a corrected tetralogy of Fallot: emphasis on the right ventricular outflow tract. Radiology 2005;in press. 50. Petersen SE, Voigtlander T, Kreitner KF, Kalden P, Wittlinger T, Scharhag J, Horstick G, Becker D, Hommel G, Thelen M, Meyer J. Quantification of shunt volumes in congenital heart diseases using a breath-hold MR phase contrast technique--comparison with oximetry. Int J Cardiovasc Imaging 2002;18:53-60. 51. Meijboom LJ, Groenink M, van der Wall EE, Romkes H, Stoker J, Mulder BJ. Aortic root asymmetry in marfan patients; evaluation by magnetic resonance imaging and comparison with standard echocardiography. Int J Card Imaging 2000;16:161-168. 52. Paelinck BP, Lamb HJ, Bax JJ, Van der Wall EE, de Roos A. Assessment of diastolic function by cardiovascular magnetic resonance. Am Heart J 2002;144:198-205. 53. Roest AA, Helbing WA, Kunz P, van den Aardweg JG, Lamb HJ, Vliegen HW, van der Wall EE, de Roos A. Exercise MR imaging in the assessment of pulmonary regurgitation and biventricular function in patients after tetralogy of fallot repair. Radiology 2002;223:204-211.

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54. Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, Bundy J, Finn JP, Klocke FJ, Judd RM. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 1999;100:1992-2002. 55. Moon JC, McKenna WJ, McCrohon JA, Elliott PM, Smith GC, Pennell DJ. Toward clinical risk assessment in hypertrophic cardiomyopathy with gadolinium cardiovascular magnetic resonance. J Am Coll Cardiol 2003;41:1561-1567. 56. Kuehne T, Saeed M, Higgins CB, Gleason K, Krombach GA, Weber OM, Martin AJ, Turner D, Teitel D, Moore P. Endovascular Stents in Pulmonary Valve and Artery in Swine: Feasibility Study of MR Imaging-guided Deployment and Postinterventional Assessment. Radiology 2003;226:475-481. 57. Razavi R, Hill DL, Keevil SF, Miquel ME, Muthurangu V, Hegde S, Rhode K, Barnett M, van Vaals J, Hawkes DJ, Baker E. Cardiac catheterisation guided by MRI in children and adults with congenital heart disease. Lancet 2003;362:1877-1882.

C h a p t e r

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Disparity between dobutamine stress and physical exercise magnetic resonance imaging in patients with an intra-atrial correction for transposition of the great arteries Thomas Oosterhof Igor I. Tulevski Arno A.W. Roest Paul Steendijk Hubert W. Vliegen Ernst E. van der Wall Albert de Roos Jan G.P. Tijssen Barbara J.M. Mulder

J Cardiovasc Magn Reson 2005;7:383-9

ABSTRACT Background In patients with an intra-atrial correction for transposition of the great arteries (TGA) an abnormal response to stress testing is common. However, hemodynamic responses may vary substantially when different stress tests are used. We compared the hemodynamic response to dobutamine stress with the response to physical exercise in patients and controls. Methods Thirty-nine patients and 25 age/sex-matched control subjects underwent either dobutamine stress (15 µg/kg/min) or submaximal physical exercise cardiovascular magnetic resonance. End-systolic and end-diastolic right ventricular volumes (ESV;EDV) were determined. Five representative patients underwent both stress tests. For these patients, wall thickening reserve was calculated as systolic wall thickening during stress minus systolic wall thickening at rest.

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Results In controls, dobutamine stress and physical exercise showed similar responses: stroke volume, cardiac output and ejection fraction increased significantly whereas ESV decreased significantly and EDV was unchanged. In patients, stroke volume did not increase with either dobutamine or exercise (-8.6% versus 2.9%). Ejection fraction increased significantly with dobutamine (16%, p