© 2014, Wiley Periodicals, Inc. DOI: 10.1111/echo.12566

Echocardiography

REVIEW ARTICLE

Evaluation of Right Ventricular Function in Adults with Congenital Heart Defects Claudio Bussadori, M.D., Ph.D.,* Giovanni Di Salvo, M.D., Ph.D.,† Francesca R. Pluchinotta, M.D.,* Luciane Piazza, M.D.,* Giampiero Gaio, M.D.,‡ Maria Giovanna Russo, M.D.,‡ and Mario Carminati, M.D., F.E.S.C., F.S.C.A.I.* *Pediatric Cardiology and Adult with Congenital Heart Disease Department, IRCCS San Donato Hospital, Milan, Italy; †Heart Institute, Pediatric Cardiology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; and ‡Department of Cardiology, Division of Pediatric Cardiology, Second University of Naples–Monaldi Hospital, Naples, Italy

The right ventricle (RV) is of lesser importance in acquired heart disease, but its role is of increasing importance in congenital heart disease (CHD). Despite major progress being made, precise measurements of the RV are challenging because of its peculiar anatomical structure that is not adaptable to any planar geometrical assumption. This is particularly true in adult patients with CHD where the RV shape eludes any standardization, it may assume various morphologies, and its modality of contraction depends on previous surgical treatment and/or pathophysiological conditions. However, reliable and repeatable quantification of RV dimensions and function for these patients are essential to provide appropriate timing for intervention to optimize outcomes. In this population, echocardiographic evaluation should not be limited to an observational and subjective functional assessment of the RV but must provide quantitative values repeatable and clinically reliable to help the decision-making process. The aim of this review was to discuss the echocardiographic approach to the RV in adult patients with CHD in general and in specific cases of pressure or volume overload. (Echocardiography 2014;00:1–15) Key words: tetralogy of Fallot, atrial septal defect, congenital heart defects, Doppler myocardial imaging, three-dimensional echocardiography, right ventricular function

The large majority of the echocardiographic studies focus on the analysis of left ventricular function and dysfunction. This is understandable as most of the acquired cardiac disease involves primarily the left ventricle (LV), and for a long time the right ventricle (RV) was overlooked. Indeed the RV was often described as the forgotten,1 neglected,2 or probably even more appropriately, the misunderstood ventricle.3 By the second half of the last century, the outcome and survival of patients with congenital heart diseases (CHDs) improved significantly. This created a new population of young patients who need lifelong follow-up, particularly addressing the anatomical and functional adaptation of the RV to the hemodynamic changes induced by surgical and interventional treatment. Reliable and repeatable quantification of dimensions and function Address for correspondence and reprint requests: Claudio Bussadori, M.D., Ph.D., Pediatric Cardiology and Adult with Congenital Heart Disease Department, IRCCS San Donato Hospital, Milan, Italy. Fax: +39-0252774328; E-mail: [email protected]

for these patients are essential to provide appropriate timing for intervention, follow-up, and reintervention.4 Two-dimensional (2D) echocardiography facilitates assessment of LV size and function, and reliable mathematical models can be applied because it has a prolate ellipsoid shape. In contrast, precise measurements of the RV are challenging because of its peculiar anatomical structure that is not adaptable to any planar geometrical assumption. The RV is composed of 3 anatomic and functional subunits (the inflow, the apex, and the outflow) that are on different spatial planes and can never be visualized at the same time with 2D techniques. Furthermore, its “peristaltic” contraction5 is not easily quantifiable with any of the newest technology. Despite these difficulties, complete guidelines on echocardiographic assessment of the RV have been published.6 These guidelines were developed for acquired cardiac disease and their usefulness in the evaluation of the RV in adult patients with congenital heart disease (ACHD) is still unvalidated. However, many of these simple quantitative 1

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indices may be useful for serial follow-up of patients, especially those with four-chambered hearts. Visual estimation of RV size and RV systolic function are less accurate and have more interobserver variability than simple dimensional quantification methods when compared to cardiac magnetic resonance (CMR).7 The aim of this review was to discuss the echocardiographic approach to the RV in ACHD in general and in two specific cases of ostium secundum-type atrial septal defect (ASD), and repaired tetralogy of Fallot (ToF). Echocardiographic Indexes of Right Ventricular Function in ACHD: The more standardized dimensional measures of the RV function include planar and linear indices such as RV wall thickness, RV inflow and outflow tract dimensions, fractional area change (FAC), pistand tricuspid annular plane systolic excursion (TAPSE). Doppler-derived indices include right ventricular myocardial performance index (RVMPI), isovolumic acceleration time, and peak systolic myocardial velocity (S’) measured with myocardial Doppler at the tricuspid annulus. The clinical applicability and interpretation of most of these measurements have been studied in ACHD and many of them are frequently used in daily practice. Thickness of the RV wall should be

measured in M-mode echo or 2D modes, either in apical, parasternal, or subcostal views. Measurements must be taken where there is less variability: at the level of the tricuspid chordae tendinae at the base of the RV wall during late diastole. To optimize image quality, it is important to accurately regulate the near gain and use a high-frequency harmonic imaging probe, to distinguish right ventricular myocardium from epicardial fat thickness of the RV; measured in this way RV wall thickness should not exceed 5 mm. The diameter and area of the right ventricular inflow tract should be measured on an apical four-chamber view optimized for the RV. In this view, it is possible to measure in late diastole 3 standard diameters: 2 transverse diameters, 1 at the tricuspid annulus RV1 (reference values: 33– 35 mm) and the other one at apex of papillary muscles RV2 (reference values: 23–33 mm), and 1 longitudinal diameter from the center of the tricuspid plane to right ventricular apex (reference values: 67–75 mm) (Fig. 1). In adult patients with distorted right ventricular morphology, the identification of the apex of the papillary muscles is often difficult and their insertion is variable, making RV2 less reproducible. In addition, the length of the RV can be very variable, especially in very dilated ventricles, and apical scanning dedicated to the RV can often be “shortened”

Figure 1. Measure of the three standard diameters of the right ventricular inflow.

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without highlighting the true apex but merely a portion of the inlet free wall. The right ventricular outflow tract (RVOT) and main pulmonary artery dimensions can be measured in a short-axis view from either the parasternal or subcostal window. The transverse diameter of RVOT should be mapped out by a line drawn from the right ventricular septum to the RVOT anterior wall at the level of the right coronary cusp (reference values: 27–30 mm) (Fig. 2). The pulmonary annulus diameter (reference values: 17–26 mm) and main pulmonary artery diameter proximal to the arterial bifurcation can be measured in the same views.6 In our experience, these measurements can consistently be applied in ACHD, but RVOT and main pulmonary artery dimensions in adult patients are optimally measured in a short-axis view from a parasternal location. Subcostal view provides suboptimal images in adults due to poor acoustic window, and the structures measured are usually parallel to the ultrasound beam with even poorer resolution. FAC of the RVOT is a simplified indirect indicator of RV systolic function obtained by calculating the percentage of systo-diastolic variation in RV area measured in a dedicated four-chamber view. Reference values for FAC in normal adults are in the range between 47% and 51%, but some authors have reported much wider values from 35% to 63%.6, 8, 9 FAC suffers for some limitations: it includes only the RVOT and the optimal view for taking the measurement is sometime variable. Nevertheless, this simplified method should be taken into consideration as it demonstrates a good correlation with RV ejection fraction (EF) measured by CMR.10. Real time three-dimensional echocardiography (RT3DE) may also investigate anatomical and functional remodeling of the RV in ACHD

Figure 2. 1 Right ventricular outflow tract diameter, 2 Pulmonary annulus diameter, 3 Main pulmonary artery diameter.

through a segmental approach. Introduction of newest postprocessing software dedicate to the RV allow its quantitative and morphological analysis.11 Most of the study on this population are on patients with repaired tetralogy of Fallot.12 Measure of right ventricular volume with RT3DE demonstrated excellent repeatability suggesting applicability for serial follow-up of patients with right heart congenital disease, but once compared with CMR limitations of RT3DE become evident. This is especially true in case of very dilated RVs where the field angle of the probes currently available often makes the inclusion of the entire RV in a single volume difficult.13 TAPSE is still widely used to study RV systolic function even if its reliability is controversial.14,15 TAPSE is acquired by placing an M-mode cursor through the tricuspid annulus and measuring the amount of longitudinal motion of the annulus at peak systole (Fig. 3). TAPSE values less than 16 mm are considered indicators of reduced systolic function. This index does not require any sophisticated software and it is generally feasible even with very low-quality images. The main disadvantage is its angle dependence. TAPSE correlated strongly with radionuclide angiography16 with low inter-observer variability. Assuming TAPSE as a marker of the RV systolic function, we accept that the displacement of the basal and adjacent segments in the apical four-chamber view is representative of the function of the entire RV. This assumption is not always valid especially in case of regional RV wall-motion abnormalities. In a small group of adult patients with repaired ToF, TAPSE was compared with RVEF and segmental right ventricular function calculated with MRI.17 In this study, regional wall-motion abnormalities reduced the accuracy of TAPSE index reducing the already low correlation with RVEF measured by CMR, and find it not reliable in repaired ToF. Myocardial performance index (MPI)18 was initially used to study global LV function19 and has now been applied also to the RV.20 The index is based on the formula [(a b)/b], where (a) is the diastole-to-diastole time and (b) is the systolic time. These intervals are measured with Doppler flow. The diastole-to-diastole time (a) is measured at the tricuspid annulus from the end of diastolic flow to the beginning of the next tricuspid flow, while the systolic time (b) is measured at the pulmonary annulus from the beginning to the end of the pulmonary flow envelope. MPI is a feasible and reproducible indicator of global function and its value increases with decreasing right ventricular function. The upper reference limit for the right-sided MPI is 0.40 using the pulsed Doppler method and 0.55 using the 3

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Figure 3. Tricuspid annular plane systolic excursion (TAPSE), The systolic peak of this excursion must be measured on the leading edge visible for all the cardiac cycle.

Figure 4. Referring points for measure of RMPI with myocardial Doppler. a is the time occurring from the end of diastole to the beginning of the next diastole definable also as tricuspid closing opening time (TCO) and include isovolumic relaxation time (IVRT) and isovolumic contraction time (IVCT). The Index is calculated with the formula: RIMP = a b/ b = (TCO ET):ET = (ICT + IVRT):ET.

pulsed tissue Doppler method6 (Fig. 4). MPI avoids the geometric assumptions and limitations of complex RV geometry, but is unreliable when RV ejection time ET and TR time are measured 4

with differing RR intervals, as in atrial fibrillation or when RA pressure is elevated because of its load dependence. Isovolumic myocardial acceleration (IVA) is derived by dividing the myocardial isovolumic peak velocity by time-to-peak velocity measured with TDI at the tricuspid annulus. It is considered as one of the less load-dependent indicators of right ventricular systolic function.21,22 IVA has been used to study severity of right ventricular dysfunction in various CHD conditions.23–26 Definition of the reference values for this index is very wide as they are influenced by age and heart rate, with a large variability. The lower reference limit obtained by TDI pooling data from 10 studies is 2.2 m/sec,2 with a broad 95% confidence interval of 1.4 to 3.0.6 This index3 may be useful in the follow-up of a single patient in particular clinical settings but because of this variability could not be considered for screening purpose. Systolic velocity of the tricuspid annulus can be assessed with pulsed-wave Doppler (PWD) or with color-coded TDI (Fig. 5) in both cases simply placing the sample volume or region of interest cursor (ROI) on the tricuspid annulus or at the middle of the basal segment of the

Right Ventricular Function in ACHD

Figure 5. Myocardial velocities measured placing sample on the tricuspid annulus. Isovolumic acceleration (IVC) peak velocity, Isovolumic myocardial acceleration (IVA) is derived dividing the peak velocity by time to peak velocity. S’ peak systolic velocity. On the left a normal young adult, on the right a young adult with a severe right ventricular dysfunction. E = early diastolic velocity. A = late diastolic velocity.

RV Wall. The values obtained with color TDI are lower than those measured with myocardial PWD because the encoded data represent mean velocities. Reference values derived from a population of young adults demonstrate mean annular velocities of 8.5–10 cm/sec, and slightly higher for basal RV free wall velocities at 9.3–11 cm/sec. Values of S’ less than 10 cm/sec suggest abnormal systolic function.6 In ACHD patients, TAPSE and S’ values must be interpreted with caution, i.e., in case of severe RV volume overload as in large ASD or severe tricuspid regurgitation, as they may present very high TAPSE values and the mild level of systolic insufficiency could not be identified. Right Ventricular Deformation Index in ACHD: All the traditional echocardiographic indices reported above are based on changes of RV dimensions or volumes or on myocardial velocities and are only indirect indicator of cardiac function. As mentioned before, it is difficult to adapt the RV morphology to any of the proposed geometrical model and this is particularly true in ACHD patient, where RV shape elude any standardization and may assume various morphologies, and the modality of contraction depend on previous surgical treatments and pathophysiological conditions. Direct interrogation of myocardial function may overcome this limitation. The advent of color TDI has allowed direct measures of myocardial deformation, at least in the longitudinal direction. With this technology, strain is obtained by temporal integration of strain rate curves that are in turn derived by the velocity gradient between 2 points where velocities are measured simultaneously.

Tissue Doppler Imaging technology has the advantage of a high temporal resolution but several disadvantages limit its application. One significant limitation is the angle dependence that restricts its real applicability only at basal and mid- segments on the apical and long-axis views.27,28 However, newer technologies are able to track myocardial motion from the 2D image independent of insonation angle.29 The advantage of angle independence is crucial to obtain information about myocardial deformation in any spatial direction, and allow quantification of various parameters such as myocardial displacement and timing (essential for synchronicity studies30), or the longitudinal radial and circumferential strain and strain rate (SR) for detailed systolic and diastolic function as well as the rotation and the rotation velocity for left ventricular torsion.31 As 2D strain technologies are independent from insonation angle and from any geometrical assumption they are ideal for quantification of RV myocardial function, particularly in cases of CHDs. Unfortunately, their application in the “real world” of our echo laboratories is not as easy as it appears. All the algorithms for strain and SR are commercially released to study LV function although they have been applied extensively “off label” to the RV. As none of the available 2D strain software includes a template for the study of RV, we apply the template for apical four-chamber view of the LV and arbitrarily divide the lateral wall into basal, mid-, and apical segments (Fig. 6). As for the LV, the selection of the appropriate echocardiographic view is crucial, but the apical 5

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Figure 6. Right ventricular longitudinal strain in a 25-year-old patient operated for tetralogy of Fallot with right ventricular dysfunction. Right bottom tracking points position on subendocardial fibers. Right top color-coded strain rate of the segment analyzed starting from basal lateral (bottom) to basal septum (top). Middle bottom SR curves, middle top strain curves. Left: report of strain values by segments ordered with left ventricle (LV) four-chamber template for which the label of septal segment refers to lateral wall and those of the later wall refer to septal segments. (Figure produced using X-Strain, Esaote, Florence, Italy.)

four-chamber view optimized for the RV is less clearly standardized. The operator should pay attention to optimize this view always in the same way as for measurements of right ventricular areas, to avoid too oblique views that may foreshorten the longitudinal axis of the RV. As this can reduce the measured RV area,6 it may also result in underestimation of right ventricular longitudinal strain. Furthermore, different algorithms may give different results and encounter different technical problems once applied to the RV. The 2 most used 2D strain technologies are “speckle tracking,” and “feature tracking” which use different algorithms. Speckle tracking imaging uses a region of interest of approximately 40 pixels32 and provides averaged transmural data grouped by segments. In the case of reduced thickness of the right ventricular wall, speckle tracking may fail to track the myocardial movements. More novel speckle tracking algorithm may work on reduced kernel33 or feature tracking,34 which is based on a mono-dimensional technology that use definitively smaller speckles, may overcome this problem and follow better the myocardial motion. A smaller kernel area may offer more detailed information about septal strain, analyzing separate activity of left or right side septal fibers. Longitudinal strain and SR of the RV 6

describe intrinsic functions and compared to other dimensional parameters are less load dependent. Nevertheless, strain compared to SR appeared to be more sensitive to volume load changes.35 In RV with chronic pressure overload, longitudinal strain as well as transversal or radial strain should be evaluated for an appropriate follow-up and this could easily be done in the apical four-chamber optimized for the RV (Fig. 7). Short-axis views of the right ventricle suitable to apply the algorithm for radial strain are obtainable only in rare cases with severe RV hypertrophy. The difficulty in obtaining repeatable good quality images of the RV, and the differences in algorithms are probably some of the major causes of the large variability in the proposed reference data.6,36,37 For this reason, RV strain is not recommended for routine clinical use but only in specific situation such as CHD and in laboratories that have already stored a pool of reference values obtained by the same operator with the same technology, or can be used in the follow-up of the same patient. Certainly strain and strain rate of the RV measurements require further studies not only for specific validation but also to better understand the physiological adaptations in myocardial deformation to changes in loading and chronic

Right Ventricular Function in ACHD

Figure 7. Right ventricular transversal strain in a 25-year-old patient operated for tetralogy of Fallot with right ventricular dysfunction. Right bottom tracking points position on subendocardial and subepicardial fibers. Right top: color-coded transversal strain of the segment analyzed starting from basal lateral (bottom) to basal septum (top). Left bottom: transversal SR curves, Left top: transversal strain curves. (Figure produced using X-Strain.)

remodeling, which is a prerequisite for understanding pathologic adaptations in CHD.38 Atrial Septal Defect: In adult patients, the ostium secundum (OS2) is the most common type of ASD. In the presence of an OS2 ASD with a hemodynamically significant shunt, all echocardiographic indices of volume overload are increased and in almost all cases, these begin to diminish significantly 24 hours after the closure of the defect.39 In the apical four-chamber view, the RV diastolic area appears augmented and the RV diameter at the tricuspid level generally exceeds 40 mm. TAPSE and systolic myocardial velocity are both increased.40 Diastolic paradoxical septal motion is always present when the RV volume overload is consistent. This condition generally disappears fairly soon after the closure of the defect. Tissue Doppler Imaging measures of the RV diastolic function may reveal anomalies not identified with PWD of tricuspid flow. Both E’ and A’ velocities are increased in ASD patients and decrease rapidly after closure in young adults. Older patients with long-standing volume

overload may show abnormal velocities of myocardial relaxation even with normal tricuspid flow. The dysfunction, once established, seems to be volume independent and does not change after device closure, suggesting altered myocardial structure and function.41 RV reverse remodeling after closure is very prompt in pediatric patients but is often incomplete in older patients (>40-year-old) undergoing transcatheter closure.42 Longitudinal strain is related to volume load, while SR reflects more the contractility. In the adult population with significant ASD, the longitudinal strain but not SR, is frequently increased and this is more evident on the RV lateral wall rather than septum. Approximately 24 hours after device closure,35 all load-dependent parameters reflect loading change in both right and LV: longitudinal strain decrease significantly, while RV SR decreased only at the lateral wall level but not at the right septum. Left ventricular end-diastolic volume and left ventricular cardiac output measured by 2D echocardiography, and global circumferential strain at mitral level both increase significantly. Longitudinal strain of the RV works 7

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as indicator of right ventricular function dependent on loading conditions, while SR seems to be less dependent on it. Circumferential strain could be used as an indicator of left ventricular response to normalized loading conditions. Postoperative Status of Adult with Tetralogy of Fallot: Adult patients operated on for ToF represent one of the most numerous groups in the ACHD population. Many of these patients frequently need a reintervention, usually related to the surgical remodeling of the RVOT such as residual pulmonary stenosis or, more frequently, pulmonary regurgitation (PR). This particularly affects the RV function, which could also be impaired by other concomitant conditions such as peripheral pulmonary stenosis, and increased pulmonary vascular resistance that worsen PR. Complete surgical correction of ToF, depending on native anatomy and surgical preference, may include infundibulectomy and/or transannular patching possibly resulting in PR and RVOT changes such as RVOT aneurismal dilation and enlargement of the pulmonary annulus. This condition may result in progressive right ventricular dilation and dysfunction. Long-standing chronic RV volume overload also affects the RV inflow tract by tricuspid annulus dilation and results in different degrees of tricuspid regurgitation. According to the ESC guidelines,43 CMR is the method of choice for assessment of RV volume and function, PR, pulmonary size and shape, and dimension of the pulmonary arteries, size of the ascending aorta, and the position of the great vessels or the conduit in relation to the sternum (resternotomy)44 but so far echocardiography is the first-line diagnostic technique. One of the most important questions regarding adult in postoperative status with PR is the quantification of RV function to indicate the most appropriate timing for pulmonary valve replacement (PVR). Several authors purposed CMR measure of RV volumes as the main indicator for PVR: RV end-diastolic volume >170 mL/m2 or RV endsystolic volume >85 mL/m2 have been proposed as a cutoff for reoperation to obtain substantial RV “normalization” after surgery.45 Other authors46 correlated RV volume, cardiac output, and exercise test changes after PVR and proposed a relatively more aggressive PVR policy (end-diastolic volume 30%).58 An end-diastolic no flow period >80 msec is equally sensitive and specific for significant PI by angiography.56 It may be more useful in adults who generally have a lower heart rate than younger children in which the duration of diastole may limit its utility.56 Restrictive Right Ventricle: Right ventricular restrictive physiology is observed in adult patient operated on for ToF. It could occur due to increasing myocardial stiffness in a severely hypertrophied and fibrotic RV but could also result from decreased ventricular compliance as in severely dilated RV.57,59 Spectral Doppler may be used to identify this condition. Because of the restrictive diastolic dysfunction, the regurgitant flow has an early peak and an early end similar to that seen in severe PR, although in this case the regurgitant flow is attenuated by an increase in the diastolic pressure

Figure 9. Pulmonary regurgitant flows (arrow) the rapid decreasing of the velocity indicate a rapid increasing of ventricular diastolic pressure.

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in mid-to-late diastole that overrides the pulmonary artery pressure. This gradient is recognized as an end-diastolic forward flow (EDFF) through the pulmonary valve just after the atrial contraction (Fig. 10). EDFF can be identified during inspiration even in normal people and for this reason, to define a RV restriction, the late diastolic anterograde flow should be recorded throughout the entire respiratory cycle: if respiration is not monitored the identification of EDFF in at least 3 consecutive cardiac cycles can be considered pathognomonic of RV restriction. Restrictive physiology may limit the degree of PR and thus can have a protective effect on RV by reducing the effect of volume overload on right ventricular dimensions.60 Severity of preoperative pulmonic stenosis and older age at time of intervention influence residual RV hypertrophy and fibrosis and they represent the most important predisposing factors to a restrictive physiology of the RV.61 Right Ventricular Morphology and Function: Adult patients operated on for ToF need periodical evaluation of their postoperative status and

echocardiography plays a cardinal role in their follow-up. Some of the echocardiographic indices described in this article can be used for this purpose, but interpretation of the results must be done considering peculiarities of the RV in ToF patients and its complex pathophysiological history. The myocardial structure is congenitally abnormal, and hypertrophy and fibrosis are present at birth and generally persist after surgical repair. Consequently, depending on the native anatomy and surgical approach adopted for the pulmonary stenosis, the RV will conserve or even increase its concentric hypertrophy if residual stenosis is present, or alternatively will start to dilate secondary to severe PR. Later in life, patients who develop RV dysfunction may require a surgical RV to pulmonary artery conduit to be implanted to maintain adequate RV function. This conduit may degenerate over time, usually resulting in various degrees of stenosis and consequent pressure overload. At this stage, patients should undergo a second surgical intervention to substitute the conduit, or a replacement with a percutaneous implant of a bovine jugular vein valve mounted on an expandable stent.62 In all these stages, one

Figure 10. The arrow indicates the end-diastolic forward flow (EDFF) recorded with CW Doppler trough the pulmonary of a restrictive right ventricle.

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of the main problems for the echocardiographist is to be able to assess the residual ventricular function in a reliable manner. However, the complex physiopathology changes that occur with several periods of volume and pressure overload, as well as the morphological and functional changes of the RV make it very difficult to determine which is the most appropriate technology or index to time surgery or intervention. FAC is used to estimate RV volumes and function in ToF.51 In all cases, it must be remembered that its geometric assumptions do not take into consideration RVOT dimension that in some patients with PR could be extremely dilated. Dimension and radial contraction of the RVOT can be assessed by measuring the fractional shortening of the RVOT (FS-RVOT) at the level of the aortic valve.6,63 Nevertheless, ventricular end-diastolic area indexed to body surface area showed good correlation with the same measure obtained by CMR even in patients who have been operated on for ToF.52 Applicability of RMPI (Right Myocardial Performance Index) in these patients is somewhat limited. RMPI from myocardial Doppler is obtained by positioning the sample volume at the lateral border of the tricuspid annulus and data are derived from temporal measurements (Fig. 4) with the obvious advantage of major precision and better sensitivity. In patients with significant PR and decreased RV compliance, there is an increased isovolumic contraction time (ICT) and decreased isovolumic relaxation time (IVRT) with a consequent paradoxically reduction in RIMP.64 RIMP derived from myocardial Doppler65 has been compared with the MRI-derived RVEF in 57 adults with repaired ToF and a negative linear correlation between the RMPI and the RVEF (r = 0.73, P < 0.001) was noted. RMPI values of 0.4 were indicative of EF lower than 35% and when lower than 0.25 were predictive of RV EF of 50% or higher. As this technology is Doppler based, its major limit as reported above is angle dependence66 TDI-derived data are less loaddependent than data derived from Doppler flow analysis. In a group of 124 patients after ToF repair, longitudinal strain TDI based and isovolumic acceleration time (IVA) data (Fig. 5) obtained at the tricuspid annulus and/or right ventricular basal segments were compared with normal controls.24 This study demonstrated the utility of measuring myocardial acceleration during the isovolumic contraction as this was noted to be lower. In all patients, IVA was lower than in controls and was correlated with the severity of PR. The extreme variability in IVA even in normal subjects does not allow reference values to be defined, which limits the use of this index to the follow-up of individual cases.

Two-dimensional strain allows computation of myocardial deformation at any level and in any direction. This can be useful in ToF patients as their RV structure have different patterns of fiber orientation and contraction and the pathophysiological events affect the RV and LV longitudinal strain,67 RV transversal strain, and LV twist68 in different ways. Furthermore, 2D strain is possible to distinguish longitudinal deformation of the right and left ventricular septum.69,35 Analysis of strain and strain rate values during the follow-up of these patients has allowed a better understanding of RV remodeling and changes in RV function. Children and young adult operated on for ToF with varying degrees of asymptomatic PR have right lateral wall and right septal wall longitudinal strain values lower than normal with a strong inverse correlation between peak systolic strain of basal lateral wall and QRS duration. This abnormality of RV longitudinal strain is more evident in patients with a transannular patch than in those with infundibular patches.67 Right ventricle dilatation is often present in operated ToF and is due to remodeling through volume overload induced by PR and sometime by afterload mismatch caused by conduit stenosis. In these patients, RV volume overload occurs in an already altered structure with various degrees of fibrosis, wall stress, and PR affecting the prevalent subendocardial fibers70 which are the major determinant of longitudinal strain. Decreasing longitudinal strain of the RV (Fig. 6) is correlated with RV dilatation and the severity of PR. In ToF, low longitudinal strain is found even in restrictive RV but because of the coexisting hypertrophy of the transverse fibers. A more correct evaluation of systolic function should be done by measuring right ventricular transversal strain (Fig. 7). In patients that undergo percutaneous pulmonary valve (PPV) implant, longitudinal strain of the RV increases significantly after the procedure but do not usually reach normal values.71,72 In our experience, in patients treated with PPV, RV longitudinal strain improved significantly 24 hours after the procedure and continues to improve at 3, 6, 12, and 24 months. In these patients, we also found a significant correlation between preprocedural longitudinal strain and performance at cardiopulmonary exercise test. Preprocedural values of longitudinal strain greater than 13% were predictive of a postprocedure VO2max > 60% of the expected value, with 83% of sensitivity and 100% specificity36. RV–LV Interaction after ToF Repair: Studies that used quantitative methods to assess ventricular function after ToF repair have mainly focused on RV mechanics and its interaction with PR, and on the presence of an akinetic or aneu11

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rysmal RV outflow tract wall. Recently, Davlouros et al.73also found a significant correlation between RVEF and LVEF and pointed out the importance of ventricular–ventricular interaction in patients with repaired ToF. The right and LVs function in series and, in the absence of shunts, have similar net outputs. In 1910, the French physiologist Bernheim first recognized interdependence between LV and RV function, and many subsequent studies demonstrated that alterations in the size and function of the LV adversely influence the geometry and function of the RV, and vice versa. Ventricular– ventricular interaction occurs because the ventricles share myofibers74 septum, coronary blood flow, and pericardial space. The superficial spiraling layer of RV myofibers is continuous with the superficial layer of the LV, whereas the deep layer of RV myofibers is continuous with that of the LV through the interventricular septum. Through a complex interplay involving the shared myofibers, septum, pericardium, and coronary flow, RV volume load leads to septal shift toward the LV, leftward shift of the LV pressure–volume loop, and reduction in LV operant volumes. Initially, LV function is preserved but with progressive RV dysfunction, LV function deteriorates. A clinical study using CMR in patients with repaired ToF demonstrated that although moderate or severe RV systolic dysfunction is an important independent factor associated with poor clinical status, late after ToF repair, RV mechanics are only part of the problem. When all variables associated with poor clinical outcome in their cohort were included in a multivariate analysis model, moderate or severe LV dysfunction was the strongest independent variable.75 Similarly, Ghai et al.76 demonstrated in a study of adults with repaired ToF that moderate or severe LV systolic dysfunction is an important risk factor for sudden cardiac death. Ventricular–ventricular interaction in patients with corrected ToF has been studied even using 2D speckle tracking, to asses global and regional RV and LV strains and LV twist. In a prospective study,68 32 patients operated on for ToF. Global RV strain, global LV strain, and LV twist were decreased and the strong correlation between these parameters confirmed the presence of adverse ventricular–ventricular interaction. Conclusions: A modern medical approach to ACHD patients should be focused on a close observation of right ventricular function and its interaction with left ventricular function on which depend prognosis and decisions about complex diagnostic and therapeutic plans. All diagnostic techniques applied in these patients, such as cardiopulmo12

nary test, CMR, CT, hemodynamic studies, electrophysiology, and biochemistry studies, provide quantitative data. Echocardiography is the most frequently performed in the follow-up and should not be limited to observational and subjective functional assessments of the RV but must provide quantitative values that must be as repeatable, clinically reliable, and useful to compare with other quantitative values. The use of new echocardiographic technologies may offer some advantage over the criteria for quantification based on 2D echo changes, but the interpretation of these results must always take into account the anatomical complexity and pathophysiology of these diseases. The validation studies of these new echocardiographic technologies, such as 3D echocardiography or 2D strain and the technological improvement of these technologies themselves appear to be such as to encourage their clinical use, however, other clinical trials will needed to define more precisely the real advantages of these new ways to asses ventricular function based on outcome data. Furthermore, the 2D strain should be used with caution in ACHD patients, because RV strain it is still an off-label use,35 and for the intervendor variability in the systems77,78 cannot be recommended for routine clinical use but only in specific situations, in experienced laboratories, and for follow-up of the same patient over time. References 1. Mertens LL, Friedberg MK: Imaging the right ventricle– current state of the art. Nature reviews. Cardiology 2010;7:551–563. 2. Stefanadis CI: Imaging of the neglected cardiac chamber: The right ventricle. Hellenic J Cardiol 2010;51:285. 3. Rudski LG, Afilalo J: The blind men of indostan and the elephant in the echo lab. J Am Soc Echocardiogr 2012;25:714–717. 4. Piazza L, Chessa M, Giamberti A, et al: Timing of pulmonary valve replacement after tetralogy of Fallot repair. Expert Rev Cardiovasc Ther 2012;10:917–923. 5. Yacoub MH: Two hearts that beat as one. Circulation 1995;92:156–157. 6. Rudski LG, Lai WW, Afilalo J, et al: Guidelines for the echocardiographic assessment of the right heart in adults: A report from the American Society of Echocardiography. J Am Soc Echocardiogr 2010;23:685–713. 7. Ling LF, Obuchowski NA, Rodriguez L, et al: Accuracy and interobserver concordance of echocardiographic assessment of right ventricular size and systolic function: A quality control exercise. J Am Soc Echocardiogr 2012;25:709–713. 8. Foale R, Nihoyannopoulos P, McKenna W, et al: Echocardiographic measurement of the normal adult right ventricle. Br Heart J. 1986;56:33–44. 9. Weyman AE. Practices and principles of echocardiography. 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 1994. 10. Zornoff LA, Skali H, Pfeffer MA, et al: Right ventricular dysfunction and risk of heart failure and mortality after myocardial infarction. J Am Coll Cardiol. 2002;39: 1450–1455.

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