Chapter 19. Right Ventricular Cardiomyopathies

The evaluation of right ventricular (RV) size and function in normal and pathologic conditions is challenging due to its complex shape and nonsymmetrical contraction. Unlike the left ventricle (LV), the RV is crescent shaped and truncated, with separate inflow and outflow portions. The normal RV is triangular (curved) when viewed sagittally, crescent shaped when viewed axially, and similar to a teapot when viewed coronally (Fig. 19–1). It is thin walled, highly trabeculated, and devoid of the LV's extensive circumferential myofibrillar architecture. The RV apex may be dominated by the shape and function of the LV apex or may be entirely separate and independent ("butterfly" apex) (Fig. 19–2).1 The RV is strongly influenced by the normally concave interventricular septum, and its shape is influenced by acute and chronic pathologic pressure and volume changes. Whereas the normal LV has the shape of a prolate ellipse (and becomes a sphere in many disease states), there is no convenient model that accurately approximates normal or pathologic RV geometry.

This chapter describes the unique characteristics of the RV and offers a comprehensive, multimodal imaging approach to the investigation of the normal and pathologic RV.

The RV is notable for its distinctive shape, heavy trabeculation, prominent moderator band, and lack of fibrous continuity between the tricuspid and pulmonic valves. The RV can be considered to be composed of three components: the inflow (or inlet), the outflow (outlet, conus, or infundibulum), and the apex. The RV inflow tract and outflow tract are separated by the thick crista supraventricularis band of muscle fibers. The apex is virtually immobile and usually tethered to the LV apex. These three parts develop separately, are independently subjected to congenital malformations, and have unique responses to pathology and pharmacologic interventions. The RV myocardium is usually 2- to 3-mm thick with subepicardial myofibers arranged in a circumferential network parallel to the atrioventricular groove, encircling the RV outflow tract (RVOT), and then becoming more spirally orientated near the RV apex.2,3 The inflow is mainly composed of circumferential fibers in the subepicardium and longitudinal fibers in the subendocardium. At the outflow tract, both subendocardial and subepicardial fibers run longitudinally. The majority of the RV myocardium is devoid of the middle circumferential myofiber array that is dominant in the LV and is much more dependent on longitudinal shortening for ejection than the LV.4 During systole, at the inflow tract, there is longitudinal shortening from base to apex and circumferential motion toward the common septum. Thus, simple global measures of RV function are difficult due to the two portions contracting perpendicular to each other.

The global RV performance is determined by the following regional contraction patterns: (1) movement of the basal free wall toward the apex (the "bellows effect"); (2) the contraction of the RVOT; (3) the contribution of the LV (tethering) at the interventricular insertion sites; and (4) the influence of the ventricular septum (interventricular dependence). Interventricular dependence is illustrated by impairment of RV function due to the adjacent diseased LV, but not necessarily due to a myopathic process itself.5 This should be considered when assessing RV performance. The evaluation of regional RV wall motion must take into consideration the variable contraction patterns near the moderator, parietal, and septomarginal bands because the muscle bundles may alter the symmetric contraction of the RV free wall (Table 19–1).

These features of RV contraction are important in understanding and estimating RV function. Because the predominant RV fractional shortening is significantly greater longitudinally than circumferentially, an evaluation of longitudinal shortening provides a relatively simple and reliable estimate of global RV function. RV function is also influenced by volume shifts that occur with normal respiration. During inspiration, venous return increases, causing an increased RV preload, with a slight but detectable increase in RV stroke volume. Therefore, when carefully measuring RV performance, one should consider whether data were acquired during inspiration, expiration, or apnea (preferred). Lastly, a regional difference in response to inotropic stimulation has been observed, with the RVOT being more reactive than the RV inflow tract.6 This may be important when evaluating response to treatment with inotropic drugs.

The LV and RV have the same stroke volume, but the upper limit of normal RV volume is greater than the LV. This explains why the normal RV ejection fraction (EF) is lower than the LVEF (example: RV in diastole, 100 mL; RV in systole, 55 mL; RV stroke volume, 45 mL; RVEF = 45/100 = 45%; LV in diastole, 90 mL; LV in systole, 45 mL; LV stroke volume, 45 mL; LVEF = 45/90 = 50%).

The pulmonary circulation normally has a low vascular resistance, and consequently, the RV has short isovolumic contraction time (ICT) and isovolumic relaxation time (IRT). The superficial circumferential fibers contract during the ICT, but during the ejection period, the deeper longitudinal fibers contract and are responsible for the longitudinal shortening. During the phase of isovolumic contraction, the longitudinal shortening of the RV occurs mainly during the ejection phase of the cardiac cycle controlled by the subendocardial fibers. Onset of RV ejection at the outflow tract is delayed approximately 25 to 50 ms after the onset of contraction of the inflow tract. These anatomic considerations provide the potential for specific regional markers of RV contractility.

In summary, RV function is difficult to assess due to its complex anatomy and physiology. Various noninvasive and invasive techniques have been used to evaluate RV function and their strengths and limitations will be discussed.

Echocardiography

Echocardiography is and will likely remain a first-line diagnostic imaging modality for evaluating the RV structure and function because of its availability and because it is a noninvasive, rapid, portable, and comprehensive approach to assess patients with suspected right heart disease. Accurate evaluation of RV morphology and function requires integration of multiple echocardiographic views, including parasternal long and short axis, RV inflow, apical four-chamber, and subcostal views.7 Although multiple quantitative methods for RV assessment are listed, assessment of RV structure and function remains mostly qualitative in clinical practice. Methods commonly used to calculate the LV volume may be used to calculate RV volumes but are less accurate due to the complex geometry. Due to these inherent limitations, a number of geometry-independent parameters have been proposed.

One-Dimensional Echocardiography (M-Mode)

The commonly reported RV internal diameter obtained with M-mode in the parasternal long axis view is an unreliable marker of RV dilation because the anterior RV wall is often poorly seen. The irregular RV shape may result in the M-mode cursor transecting either the wider central plane or a narrower peripheral site because the cursor may transect the RV in an oblique manner.

The total tricuspid annular descent or tricuspid annular plane systolic excursion (TAPSE) is an important marker of RV global systolic function (normal, 20 mm). The TAPSE can be derived from M-mode analysis of the lateral tricuspid annular ring or Doppler tissue imaging (DTI) color display (Fig. 19–3). Interestingly, for such a simple marker of RV function, the correlation between TAPSE and RVEF by cardiac magnetic resonance (CMR) was superior to radionuclide techniques and three-dimensional estimates of RVEF.8

Two-Dimensional Echocardiography

Normally, the LV appears larger than the RV in the parasternal long and short axis and the apical four-chamber view. To use this evaluation of RV size, care must be taken not to foreshorten the LV and overestimate the relative RV size (see Fig. 19–2B). For volume calculations, additional problems are encountered. During RV dilation, the already complex geometry undergoes significant and variable shape changes. Therefore, geometric formulas used for normal RV shapes are not likely to be valid in pathologic conditions. Despite attempts to obtain orthogonal RV images necessary for volume calculations, most commonly using the apical four-chamber and subcostal views, it remains difficult to validate that they are orthogonal.9

Because the RVOT is composed of a preponderance of circumferential myofibers, this region is an estimate of global RV function. The RVOT fractional shortening can be calculated as the percentage of the RVOT diastolic diameter minus the systolic diameter divided by the diastolic diameter. Either two-dimensional (2D) or M-mode echocardiography of the basal parasternal short axis view at the level of the aortic root can be used to measure this value, and this value has been shown to correlate with TAPSE. Importantly, it closely correlates with other physiologic events, such as the shortened pulmonary acceleration time recorded at the cusp level in patients with pulmonary hypertension.10

The RVEF can be determined using the area-length method applied to the apical four-chamber view or an adequate subcostal view.11 Similar to its proven value in the assessment of LV diseases, contrast echocardiography has recently been shown to be of value in evaluating the presence of RV pathology.12 Occasionally, agitated saline contrast alone may improve the visualization of the RV borders. If ineffective, a contrast agent (activated perflutren) can be administered to improve the echocardiographic assessment of the RV size and global and regional function (Fig. 19–4). When image quality is suboptimal, contrast should be administered and has been demonstrated to be safe and cost effective.13

Global, systolic RV function can be assessed quantitatively using 2D echocardiography analysis as percentage of change in the RV cavity area from end-diastole to end-systole in the apical four-chamber view. End-diastole is identified by the onset of the R wave, whereas end-systole is regarded as the smallest RV cavity size just before the tricuspid valve opening. Endocardial borders of the RV free wall and septum are traced from base to apex, and the RV fractional area change (RV FAC) is defined using the following formula: (end-diastolic area – end-systolic area)/(end-diastolic area) × 100 (Fig. 19–5). Heavy RV trabeculation makes endocardial tracing difficult and requires an adequate quality image for accuracy of this parameter. This technique incorporates the RV inflow tract and the apex but excludes the RVOT and may overestimate RV function if focal regional dysfunction exists in this region. The percentage of RV FAC is a relatively simple parameter that is a surrogate marker of the RVEF and correlates well with CMR-derived RVEF (r = 0.80).14

Conventional Doppler Techniques

Pulsed wave Doppler tricuspid flow velocity helps evaluate RV filling and, indirectly, RV diastolic function. Peak flow velocity in early diastole (E wave), peak velocity at atrial contraction (A wave), tricuspid deceleration time, and tricuspid A wave duration are variables that can be compared with their mitral counterparts to assess for unilateral or bilateral heart disease. The hepatic vein and superior vena caval flow velocities can be obtained with pulsed wave Doppler and analyzed during apnea or in response to volume changes that occur with normal respiration. Increased flow reversals in the hepatic vein (>20%) or superior vena cava (>10%) during apnea suggest increased right-sided heart filling pressures. Increased flow reversals in response to inspiration or expiration can be seen in patients with restrictive or constrictive cardiomyopathies, respectively.15-17

Because tricuspid regurgitation (TR) is common, the rate of RV pressure increase can be obtained from the continuous-wave spectral Doppler TR signal. The time interval (dt) necessary to increase the TR velocity from 0 to 2 m/s is measured (Fig. 19–6). This represents a pressure change (dP) of 16 mm Hg. The dP/dt value is considered normal if it is greater than 400 mm Hg/s.18 The accuracy of this method is directly dependent on the quality of the TR Doppler envelope. Because dP/dt is influenced by preload, adding the maximal TR velocity (Pmax) into the equation as dP/dt/Pmax compensates for changes in preload.19 In patients with dominant RV failure, TR-derived dP/dt/Pmax, but not dP/dt alone, has been identified as a clinically useful index of RV contractility.

The RV index of myocardial performance (RIMP; or Tei index) is defined as the sum of the ICT and IRT divided by the ejection time and is increased in either systolic or diastolic RV dysfunction (Fig. 19–7).20 An elevated RIMP has been shown to be an early sign of RV dysfunction in cardiac amyloidosis.21 Patients with hypertrophic cardiomyopathy and exertional dyspnea have an increased global RIMP compared to those without dyspnea.22 A value ≥0.40 has a sensitivity of 81% and a specificity of 85% to diagnose RVEF <35%. A value <0.25 has a sensitivity of 70% and a specificity of 89% to identify patients with RVEF ≥0.50.23 Doppler-derived RIMP measurement correlates with the CMR-derived RVEF and is a simple and reliable method for the evaluation of RV function in adults with repaired tetralogy of Fallot. This index is a marker of prognosis in patients with heart failure and primary pulmonary hypertension and has been used for risk stratification.24,25

Tissue Doppler Imaging

Tissue Doppler imaging of the RV is a useful and readily applicable adjunct to the comprehensive echocardiography Doppler assessment of the RV by transthoracic echocardiography. Tissue Doppler imaging permits analysis of the RV longitudinal myocardial velocity. Because the RV is composed of a network of clockwise and counter-clockwise endocardial and epicardial longitudinal myofibers, the RV myocardial velocity reflects RV systolic function. Similar to the LV, five major deflections are visualized on tissue Doppler imaging of the RV tricuspid annulus: ICT wave, systolic velocity, IRT wave, early diastolic velocity, and late diastolic velocity (Fig. 19–8). Timing of the RV events can be measured using a high frame rate, leading to an alternative calculation of RIMP (Fig. 19–9). Because short time measurements are analyzed to derive this value, it is imperative that high-quality tissue Doppler imaging tracings are obtained with satisfactory temporal resolution.

Tissue Doppler can also be used to record the peak systolic velocity of the tricuspid annulus (s′). In healthy individuals, the lower normal limit at the basal RV lateral wall is ≥14 ± 2 cm/s for DTI spectral displays and ≥10 ± 2 cm/s for DTI color displays. This velocity has been shown to correlate more closely with CMR-derived RVEF than the fractional area change (FAC), DTI-derived tissue displacement, systolic strain, and strain rate.26 An s′ <9.5 cm/s identifies patients with an RVEF <40%.27 Thresholds of >12, 12 to 9, and <9 cm/s allow differentiation between normal (>55%), moderately reduced (30%-55%), and severely reduced (<30%) RVEF, respectively.28

Myocardial velocity of the RV free wall as measured by DTI during the ICT phase has also been used to estimate RV contractility. However, this parameter is more sensitive to loading conditions than the other listed markers. Myocardial acceleration during the earliest phase of ICT is a novel index for the assessment of RV contractile function that is less affected by preload and afterload changes.29 This index is calculated by dividing myocardial velocity during ICT by the time interval from the onset of this wave to the time at peak velocity (Fig. 19–9).

Tissue Doppler measures are dependent on the Doppler cursor angle. This limitation is overcome with 2D strain measures (speckle tracking) and, being angle independent, allows the evaluation of regional function in all myocardial segments, including the ventricular apex (Fig. 19–10). Ultrasound "speckles" in the RV wall are tracked and allow the determination of the global and regional, frame-to-frame measure of myocardial velocities, 2D strain, and strain rate. Peak systolic strain and strain rate, particularly of the basal RV free wall, are significantly impaired in patients with pulmonary arterial hypertension and have been used as an index of RV function.30

The quantification of regional myocardial function remains a challenge. One main limitation of conventional DTI is that an akinetic segment may still possess measurable myocardial velocities due to being tethered to a normal adjacent myocardial segment. Strain and strain rate are indices of myocardial deformation that largely overcome this limitation. Strain rate (velocity of deformation) can be calculated from the spatial gradient in velocities recorded between two neighboring points in the tissue (Fig. 19–11).31 The longitudinal RV strain and strain rate values are higher and more inhomogeneous than those in the LV. Mean values for longitudinal strain and strain rate are lowest in the basal RV segments and increase toward the apical segments. Strain rate imaging is independent of overall motion.

The quantification of regional RV function using either 2D or DTI strain values is feasible and reproducible.32 This technique has a potential role in the initial and serial assessment of patients with primary or secondary RV disease and correlates with invasive and CMR findings of RV performance.33

Three-Dimensional Echocardiography

Three-dimensional (3D) echocardiographic analysis of the RV has recently been reported to eliminate the geometric intricacies of the RV. Due to the nongeometric 3D shape of the RV, the measurement of RV volume is challenging, resulting in numerous qualitative, but limited quantitative, measures. Recently, real-time 3D echocardiography (RT3DE) has become available and can provide reliable, reproducible measures of RV volumes independent of geometric assumptions.34 By manually tracing the endocardial borders during systole and diastole, the RV volumes are determined, and RVEF is calculated. Because an image of the entire RV is acquired in a single pyramidal data set, any acoustic window will increase the likelihood that adequate quality data are obtained (Fig. 19–12). For measuring RV volume and RVEF, RT3DE is more accurate and reproducible than 2D echocardiography and has less variation and higher correlation to CMR.35 Normal RT3DE values of the RV size and function are listed in Table 19–2.36

In a study of 200 patients, including normal controls and patients with valvular heart disease, pulmonary hypertension, and dilated cardiomyopathies, RT3DE results were compared with results from conventional 2D and RV Doppler flow and showed a positive correlation of 3D RVEF with TAPSE, FAC, and peak s′ tissue Doppler echocardiography (TDE) velocity and a negative correlation with pulmonary artery pressure.37 Adequate, good-quality 3D acquisition was obtained in nearly all patients with a mean time of 3 ± 1 minutes. The technique of RT3DE has been validated in phantoms, animals studies, adult patients with RV cardiomyopathies, and children with congenital heart diseases.38 Excellent correlation exists with magnetic resonance imaging (MRI) reference standards, although there is a common underestimation of RV volumes. Although additional data from RT3DE studies including a wider variety of RV pathologies are needed, this option appears to be the most cost-effective reference standard for quantitative RV volume and EF determination.

Transesophageal Echocardiography

In patients with suboptimal transthoracic echocardiographic windows, transesophageal echocardiography (TEE) may be considered because the esophageal window is frequently adequate for cardiac assessment. There are few studies reported on the use of this method for assessment of the RV. Most reports are from intraoperative studies where inotropic medications and rapid fluid shifts limit the interpretation of reported findings. In a study of 25 children with atrial septal defects undergoing surgical correction, 90% had adequate 3D TEE studies.39 RV volumes had an excellent correlation with direct surgical measures (r2 = 0.99), obtained at the end of surgery by injecting saline solution through the tricuspid valve using a graduated syringe, but had a slight, consistent overestimation.

If tricuspid or pulmonic valve disease is suspected, this is a valuable complementary diagnostic tool. This approach is also useful for the assessment of the atrial septum for congenital defects or to determine whether RVOT obstruction is a cause of RV dilation or dysfunction. In general, TEE is reserved for patients in whom the transthoracic echocardiogram is suboptimal, despite the use of contrast, and when CMR is unavailable.

Nuclear Cardiology

First-Pass Radionuclide Angiography

Radionuclide angiography (RNA) is the historical reference standard for RVEF and has been used to measure global and regional RV abnormalities.40 A significant advantage of this technique is its reliance on a count-based method that is independent of geometry. This technique relies on separation of the radioactivity within the RV from adjacent structures, especially the right atrium. The RVEF is calculated by tracing the RV cavity in an end-diastolic and end-systolic frame. The most accurate method to achieve this is a gated first-pass RNA. This ensures that the radioisotope remains within the RV cavity and allows acquisition of RV functional data prior to the isotope crossing the pulmonary vasculature and contaminating the field of interest with left atrial and LV radioactivity. Although nuclear scans are widely available, first-pass RNA studies are not commonly performed.

Equilibrium-Gated RNA

Multigated acquisition (MUGA) equilibrium scans are used for analysis of functional LV data but are not optimal for RV assessment and result in underestimation of the RVEF. We have found that first-pass RNA correlates better with CMR determined RVEF, as compared with gated equilibrium RNA.41

Myocardial Perfusion Imaging Single Photon Emission Computed Tomography

Myocardial perfusion imaging (MPI) using electrocardiogram (ECG)-gated single photon emission computed tomography (SPECT) is commonly performed for evaluation of myocardial ischemia. It is not used primarily to evaluate LV (or RV) function, but this information is obtained and is valuable when an ischemia assessment is performed. Its specific role in evaluating RV pathology is limited. Indirect evidence of RV dilation and RV hypertrophy may be seen as increased RV radiotracer uptake, but SPECT cannot clarify whether this is due to valvular or congenital heart disease, pulmonary arterial hypertension, or a primary RV cardiomyopathy.42 MPI is most valuable to assess LV myocardial ischemia or scar and may assist in the indirect assessment of the patient with RV cardiomyopathy.

Radiolabeled Meta-Iodobenzylguanidine Imaging

Radiolabeled iodine 123–meta-iodobenzylguanidine (123I-mIBG), also known as iobenguane, an analog of the false neurotransmitter guanethidine, is used to scintigraphically map the adrenergic system in the myocardium. This agent localizes in adrenergic nerve terminals primarily by the norepinephrine transporter and is decreased in heart failure patients with the poorest prognosis.43,44 Because sympathetic innervation of the heart participates in the regulation of myocardial contractility and because there is a link between catecholamine hypersensitivity and ventricular arrhythmias, there may be diagnostic value for predicting arrhythmic substrate in cardiomyopathies. Abnormalities of myocardial 123I-mIBG uptake have been reported to be predictive of ventricular arrhythmias and sudden cardiac death in patients with idiopathic ventricular fibrillation.45 The RV myocardium cannot be adequately studied with this agent, but coexistent LV involvement may be identified earlier than with other diagnostic modalities.

CMR Imaging

Black Blood, Static Imaging

High spatial resolution images can be obtained using spin-echo CMR sequences and ECG and respiratory gating optimized to minimize cardiac motion artifacts.46 This provides high image detail of the RV myocardium to assess cavity shape, wall thickness, and intracavitary structures such as the papillary muscles and moderator band. A fat saturation pulse can confirm the presence and extent of fat. Cardiac valves, being thinner and highly mobile, are less well visualized than they are with echocardiography (Fig. 19–13A).

White Blood, Cine Imaging

It is possible to accurately calculate both LV and RV volumes simultaneously by CMR.35,47 Both ventricles are imaged in the same acquisition, and multiple short axis slices are obtained. From each short axis slice of known thickness, the area is calculated, and the summed volumes are determined using Simpson's rule (Fig. 19–13B). This method is not dependent on acoustic windows, is not limited by geometric assumptions, and rarely has poor-quality results. CMR has excellent interstudy reproducibility in healthy subjects, patients with heart failure, and patients with hypertrophy. Quantitative RV volume and function have been validated in a large, multiethnic study.48

CMR is considered the reference standard for research investigations and for serial measures in patients with chronic heart diseases, especially involving the RV. Rarely, assessment of the RV volume may be challenging due to poor delineation of the endocardial border, especially in end-systole due to elimination of blood from intertrabecular spaces. Partial volume artifacts may occasionally reduce the quality of the RV apex. Also, the inability to visualize the pulmonic valve may overestimate RV volume by including PA volume as well. CMR is relatively contraindicated in patients with pacemakers, implantable defibrillators, cerebral aneurysm clips, and other non–CMR-compatible metallic devices. Presently, CMR is considered to be an appropriate test for evaluation of RV volume, mass, and function.49

Tagging Sequences

Although global RV volume and function are reliably measured using cine CMR, abnormalities in these parameters occur relatively late in the course of the disease. Earlier markers of RV dysfunction, frequently regional, would be valuable. There are numerous reports on the value of quantitative regional strain assessment as an early marker of many cardiac diseases. Myocardial tagging using modern CMR imaging sequences allows quantitative assessment of subtle regions of cardiac dysfunction.50 This method of regional RV wall assessment will eventually become the diagnostic reference tool of choice for subtle and/or early RV pathology.

Myocardial Delayed Contrast Enhancement

A valuable component of CMR imaging is the ability to characterize myocardial tissue using the previously mentioned sequences coupled with the infusion of gadolinium contrast. The normal and pathologic wash-out kinetics of contrast have been well validated and provide evidence of normal or abnormal myocardial tissues. Although initially established for LV myocardial diseases, this technique can also be used for the thinner walled RV myocardium, although its reliability is less well established (Fig. 19–13C).51

Multidetector Cardiac Computed Tomography

Cardiac computed tomography (CCT) provides high-quality 3D data sets for postprocessing that can be used to obtain both global and regional RV function parameters and anatomic volume with high spatial and adequate temporal resolution within a breath-hold using ECG synchronization (Fig. 19–14). The ability to assess functional information of the RV represents another important application of CCT, especially in patients with acute pulmonary emboli and congenital cardiovascular disease commonly referred for CCT. The accuracy of volume and regional functional measurements depends on the spatial and temporal resolution as well as the timing of the contrast enhancement of cardiac chambers. Optimal contrast timing requires a priori determination to maximize visualization of either the RV or LV or both ventricles equally. Reconstruction of thin myocardial slices reduces partial volume effect and provides a sharper definition of endocardial borders. Retrospective cardiac gating has the advantage of enabling image reconstructions at any point throughout the cardiac cycle and is essential for functional analysis. Few studies have been published on RV global function assessment in comparison with standard modalities. Due to the current lower temporal resolution of CCT compared with echocardiography or CMR, a slight overestimation of the ventricular volumes may be expected.52

Cine Angiography of the RV

To perform an angiogram of the RV that is suitable for both qualitative and quantitative analysis, there must be good opacification during contrast injection. Either a pigtail catheter (5-French) or Berman catheter (6- or 7-French) can be used. RV angiograms are performed in several views: (1) anterior-posterior; (2) lateral; (3) right anterior oblique (RAO) 30°; and (4) left anterior oblique (LAO) 60°. The catheter should be positioned within the chamber but not touching the walls because this can create artifact wall motion abnormalities as well as ectopic ventricular complexes. A high frame rate of 30 frames per second is preferred, with 40 to 50 mL of contrast injected at a rate of 12 to 15 mL/s.53 The patient should be instructed to hold his or her breath, and the table should not be moved. Cardiac cycles that occur just after ventricular ectopic beats should not be analyzed.

The interpretation of the RV angiogram is complex because the RV is an asymmetric chamber with nonuniform contraction. In normal subjects, the most vigorous contraction occurs in the tricuspid inflow region, which can also be measured as the TAPSE. Less vigorous contraction occurs in the inferior wall and apex, whereas the anterior wall, outflow tract, and septum have minimal contraction. A quantitative assessment of wall motion compared with normal subjects is helpful to assess the significance of segments that have a visual impression of hypokinesis.54 The RAO 30° image display is commonly used to assess RV contraction.

RV volumes and EFs can be computed from angiographic views of end-diastole and end-systole. Volume formulae based on calculation of the projected area and length in one or two fluoroscopic views have been derived based on various geometric models such as the hemi-ellipse model and pyramids incorporating projected areas from the RAO 30° and LAO 60° views or the RAO 30° view alone or in combination with area and length from anterior-posterior and lateral fluoroscopic views.55-58 For instance, the formula for volume proposed by Ferlinz57 and validated with volumes measured by water displacement of an RV cast is given as follows: Volume = 0.6☆ARAO☆ALAO/LRAO + 3.9 (mL), where ARAO and ALAO are the projected areas in the RAO 30° and LAO 60° views and LRAO is the projected distance in the RAO 30° view from the pulmonic valve to the point that bisects the inferior wall (Fig. 19–15). Commercial software is also available to compute volumes (PIE Medical Imaging, Maastricht, the Netherlands).59

Volume measurements require a calibration to a standard-sized object in the fluoroscopic view. This can be achieved with a metal ball or ruler placed on the chest or by measurement of the projected diameter of the known size of the intracardiac catheter used for injection of dye. A magnified high-resolution image of the catheter is needed because a small measurement error will translate to a large error in volume as the calibration constant is proportional to the third power of the catheter diameter. Calculation of the EF does not require image calibration. In a small series of pediatric and adult patients, there was good correlation between angiographically derived volumes and those computed from CMR imaging.59

Angiographically derived RV volume and EF have been studied in certain patient populations. In arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) subjects, angiographically derived RVEF is reduced compared with normal subjects.53,60 RV end-diastolic volumes are increased in athletes compared with nonathletes.61 In athletes with ventricular arrhythmias, the RV end-systolic volume is increased compared with athletes without ventricular arrhythmias, raising the concern that high-performance exercise may trigger arrhythmias and structural changes in the RV or unmask an early stage of ARVC/D.

Intracardiac Echocardiography

Intracardiac echocardiography (ICE) can be used to measure the RV volumes and function using a 10-MHz ICE catheter and acquiring sequential cross-sectional images from RV apex to base during a calibrated pullback.62 Volumes were calculated in an in vitro model by applying Simpson's algorithm, and these correlated well with actual volumes (standard error of estimate [SEE] = 2.3 mL, r = 0.98). Also, a beating-heart canine model was used, and findings were compared with actual volumes measured by an intracavitary balloon connected to an external column. Good correlations were observed between ICE and actual values for diastolic (SEE = 4.1 mL, r = 0.97), systolic (SEE = 3.4 mL, r = 0.96), and EF (SEE = 3.1%, r = 0.87) values. This technique has been demonstrated to accurately assess quantitative RV parameters and provides the researcher and clinician with an additional diagnostic tool.

General Approach (Algorithm)

The proposed approach is recommended based on the data presented in this review, although no imaging protocol has been proven to be superior. Initially, conventional echocardiography is used to establish a rapid assessment of the RV size and function (Fig. 19–16). Additional echocardiographic techniques are added for serial investigations or when RV size and function remain in question after the conventional approach.63 Due to the limited data on normal RV dimensions adjusted for body size and gender, the majority of these findings are qualitative, and quantitative findings are currently not sufficient to determine mild or early concealed disease. One such parameter is the estimation of RV size and function using the conventional apical four-chamber view and tracing the RV endocardium in diastole and systole to obtain the FAC. The RV image should be optimized to maximize the diameter of the tricuspid annulus and the RV length.

Complex echocardiographic techniques should be used selectively. Contrast infusion and/or TEE imaging is an option if there are suboptimal transthoracic windows. Nuclear first-pass RNA may be of value when echocardiography images are suboptimal or clinical questions remain. If CMR is available, this should be used as the reference standard for research and as an alternative to first-pass RNA when echocardiographic images are not diagnostic. When gating artifacts or MRI contraindications require an alternative reference standard, invasive RV angiography or ICE should be considered. If noninvasive coronary artery imaging is performed using multidetector CT scan, the RV can be assessed using a multiphasic reconstruction technique.

Finally, when evaluating the patient with heart failure who has a dilated RV, color flow Doppler should be performed to look for features characteristic of ASD, Ebstein anomaly, or severe TR. Conventional Doppler can establish the diagnosis of pulmonary hypertension or pulmonic stenosis. In the absence of these findings, RV infarction, ARVC/D, and cardiac contusion should be considered. Uhl anomaly is a diagnosis of exclusion. The discussion of disease-specific pathologic examples follow.

RV Dysfunction Secondary to LV Dysfunction

The most common cause of RV dysfunction is passive influence due to LV dysfunction. Therefore, any diagnostic tool for RV assessment must also be capable of adequate LV assessment. This is a significant limitation of first-pass RNA. Comprehensive biventricular imaging is possible with 2D and 3D echocardiography as well as CMR. Echocardiography Doppler has a distinct advantage of being able to evaluate the anatomy and function of the cardiac valves and indirectly assess cardiac hemodynamics.

In patients with chronic systolic heart failure (LVEF ≤45%) and moderate to severe mitral regurgitation, TAPSE is highly discriminating.64 Survival was 45% in those with the worst TAPSE, whereas it was 82% in those with TAPSE >14 mm. The RVEF is also an independent predictor of survival in patients with moderate heart failure.65

RV Infarction

The clinical triad of hypotension, elevated right atrial pressure, and clear lung fields may be due to pericardial effusion, tamponade, or acute pulmonary emboli. In addition to a specific search for ST-segment elevation in the right precordial ECG leads, global RV size and regional RV function should be assessed. This can be accomplished with portable 2D echocardiography. In addition to evaluating the RV regional contraction pattern, the presence of pericardial fluid, tamponade, and severity of tricuspid regurgitation can be observed. The parasternal short axis view shows inferior RV wall continuity and has the highest reported sensitivity (82%) for detecting a hemodynamically important RV infarction.66

RV infarction is relatively commonly associated with an ECG pattern of inferior myocardial infarction, and these patients have a poor prognosis.67 Furthermore, the diagnostic clinical constellation and the ECG findings of RV infarction are not as accurate compared with more advanced imaging techniques. Recently, it was demonstrated that delayed myocardial contrast was present in the inferior RV myocardial wall in patients with RV myocardial infarction and that this finding was significantly more frequent than either echocardiography or ECG abnormalities.68 Interestingly, these authors also found RV wall motion abnormalities in patients without RV infarction confirming that segmental RV contraction alone is not specific for RV pathology and occurs in normal controls.

Decreased RV systolic function is a major risk factor for death, sudden death, heart failure, and stroke after myocardial infarction. For every 5% reduction in FAC%, there was a 1.53 increased risk of fatal and nonfatal cardiovascular outcomes.69

RV Volume Overload

The RV can accept large volume changes acutely with minimal decrease in RV performance. Chronic RV volume overload may cause RV failure. RV volume overload in the absence of pulmonary hypertension is common in valvular and congenital heart diseases. The RV function is usually preserved because the RV initially accommodates volume overload better than an increase in pressure. It is difficult to image large RV cavities by 3D echocardiography and TEE imaging because the entire cardiac data set may be too large to be included in the imaging field. Invasive RV angiography also must adjust image acquisition (higher contrast volume, higher rate of infusion) to maintain adequate images. Regardless of the RV size or function, CMR and first-pass RNA images are usually adequate for analysis.

Congenital Heart Disease

General Overview

Although quantitative estimates of RV size and function are less accurate than the methods used for LV assessment, they are superior to the most commonly used visual, or "eyeball," assessment. In a study of 22 patients with right-sided congenital heart disease who underwent both echocardiography and reference CMR, investigators compared the interpretations of four echocardiographers. The ability of the echocardiographer to correctly classify the RV into one of four CMR-defined categories of size and function was only 50% and 41%, respectively. There was both over- and underestimation.70 RT3DE data were obtained in 28 patients with congenital heart disease and a wide range of RV size and function. The investigators used a modified apical window that enabled visualization of the RVOT and compared conventional manual measures (19 minutes) to a rapid automated technique (5 minutes). They found an excellent overall correlation of RVEF and size (r = 0.83-0.92; depending on method and parameter) but a consistent underestimation (~20 mL) of RV volumes (especially in the largest RV cavities) with CMR-derived data obtained within 2 hours of the RT3DE study.71 Although only half the study patients had adequate images for RT3DE analysis, this study lends further hope that a more accurate, automated, and rapid echo method may be available to assess the size and function of complex congenital malformations of the RV.

Atrial Septal Defect

Left to right cardiac shunting is a common cause of RV dilation. The right atrium and pulmonary artery are also dilated in atrial septal defect (ASD). If the pulmonary artery is normal, it is highly unlikely that a significant right-to-left cardiac shunt exists. In addition to diagnostic imaging modalities capable of assessing RV volume overload, there are incremental advantages of 2D and 3D echocardiography because they can assess the anatomy, size, and significance of cardiac shunting. When clinical or imaging suspicion for an ASD exists but is not confirmed, one should search for an anomalous pulmonary vein that may mimic all of the features of an ASD.

Tetralogy of Fallot with Pulmonary Regurgitation

Pulmonary regurgitation is anticipated after repair of tetralogy of Fallot, and valve replacement is recommended if the RV function begins to fail (Fig. 19–17). Complete RV recovery is less likely after significant RV dilation and dysfunction occurs. Therefore, early identification of severe RV dysfunction is important. The rate of acceleration of the RV lateral wall s′ wave by TDE has been used for this purpose.72 This index was found to be valuable in patients with tetralogy of Fallot who had variable amounts of pulmonary regurgitation (preload). Myocardial tagging with CMR should also provide an early marker of RV dysfunction but has yet to be adequately studied in this population.

Ebstein Anomaly

Apical displacement of the tricuspid valve septal leaflet insertion >8 mm/m2 is diagnostic of this entity.73 The tricuspid valve leaflet is redundant and elongated. Unlike many congenital heart diseases, Ebstein anomaly may first be diagnosed in the adult. These patients may present with exertional dyspnea and a diagnosis of cor pulmonale or similar incorrect diagnosis. Numerous masqueraders of Ebstein anomaly exist (eg, tricuspid valve dysplasia, prolapse or traumatic flail leaflet, ARVC/D), and they can be diagnosed with adequate 2D echocardiography or CMR. Endocarditis may also mimic this disease and either transthoracic echocardiography or TEE should confirm this pathology. Ebstein anomaly should be considered in the differential diagnosis of all patients with right heart dilatation.

Patent Ductus Arteriosus

A patent arterial duct in the adult is usually small and clinically silent. A moderate-sized patent ductus arteriosus is usually manifest by a continuous murmur, LV dilation, and shunt-related pulmonary hypertension. Echocardiography using 2D and Doppler flow analysis is most commonly used to make this diagnosis. In all patients with secondary pulmonary hypertension and RV dysfunction, the possible presence of a patent ductus arteriosus should be carefully evaluated by color flow Doppler.74 These shunts can be readily closed percutaneously, and this should be considered even with pulmonary arterial hypertension (pulmonary artery pressure greater than two thirds of the systemic arterial pressure; or pulmonary vascular resistance exceeds two thirds of the systemic vascular resistance) if the left to right shunt is at least 1.5:1. Cardiac MRI and CCT can provide clear 3D volume-rendered images to assist with operative interventions. Cardiac MRI can also accurately assess the degree of cardiac shunting.

Congenital Absence of the Pericardium

RV dilation is common in this entity and may mimic RV volume overload.75 Cardiac MRI and CT are excellent modalities to distinguish this cause of RV dilation due to their ability to obtain excellent pericardial images.76 It is critical to distinguish complete pericardial absence from partial absence because the latter entity places the patient at risk for cardiac herniation and fatal myocardial strangulation. Again, CMR and CCT can usually confirm the diagnosis.77

Carcinoid Heart Disease

This is a relatively rare disease that often presents with tricuspid and pulmonic valve pathology (mixed stenosis/regurgitation), with RV dilation and dysfunction. It is commonly diagnosed with transthoracic echocardiography and Doppler flow analysis. Occasionally, the valves are spared and the primary involvement is a metastatic tumor mass of the RV (or LV) myocardium.78 Diagnostic tools that can characterize the myocardium are valuable. Nuclear SPECT imaging (using the radioisotope technetium 99m and routine MPI sequencing) and CMR (T2 short tau inversion recovery) have been reported to clearly distinguish the tumor mass from the adjacent myocardium.79

RV Pressure Overload

Unlike RV volume overload, RV pressure overload (RVPO) is most commonly associated with RV dysfunction and with right ventricular hypertrophy (RVH), if chronic. The RV is unable to adequately adjust to acute pressure overload, such as due to pulmonary emboli, and acute regional RV failure, commonly with apical sparing (McConnell sign), ensues (Fig. 19–18).80 The reason for apical "sparing" may be partly related to the fact that the RV apical contraction is primarily due to LV contraction and the RV apex is pulled toward the LV, creating the illusion of normal RV contraction. The free wall of the RV, lacking the apical interventricular continuity (no "LV tethering"), is more notably dysfunctional. Gradual RV pressure overload creates less acute changes in RV size and function and provides time for some degree of RV compensation.

Both TAPSE and RIMP have been reported to correlate well with clinical, biochemical, and echocardiographic parameters of poor clinical outcomes after acute pulmonary emboli.81

Echocardiography is again the first-line diagnostic approach to assess these patients. Normal wall thickness of the RV is 2 to 3 mm and can be measured using 2D echocardiography or, less commonly, M-mode. Up to 5-mm wall thickness is usually considered normal due to difficulties in distinguishing myocardium from epicardium and confirming a perpendicular alignment. The subcostal view is the most reliable for assessment of RVH, whereas the apical four-chamber view is the least reliable. Using M-mode echocardiography in the subcostal view, a wall thickness ≥5 mm was abnormal with a 90% sensitivity and 94% specificity.82 In addition to RV volume and function assessment, continuous wave spectral Doppler of the TR jet is able to accurately assess the degree of RVPO that is not possible with other imaging tools. CCT is becoming the initial diagnostic imaging test to assess pulmonary emboli. RV enlargement identified with CT predicts early death and adverse clinical events in patients with acute pulmonary emboli.83,84

Pulmonary Hypertension Due to Left Heart Disease (Group 2)

It is difficult to differentiate pulmonary arterial hypertension (PAH; group 1) from pulmonary hypertension secondary to left heart disease (group 2), especially in patients with normal LV global systolic function. Comprehensive transthoracic echocardiographic imaging with TDE is uniquely able to provide relatively accurate, noninvasive estimates of left atrial pressure in these patients. However, if severe PAH is present and associated with RV dysfunction, then LV filling is reduced, and the accuracy of echocardiography/Doppler to differentiate primary from secondary PAH is diminished.85 Volume loading, or performing exercise TDE, may assist in this distinction. Because treatment algorithms vary based on the type of PAH, further studies are required to determine the optimal diagnostic method to confirm group 2 PAH secondary to diastolic dysfunction.

In patients with congenital heart disease (group 1 PAH) or chronic obstructive pulmonary disease (group 3 PAH) and pulmonary hypertension, DTI-derived RV strain is a sensitive index of segmental contractile function and correlates with invasively derived RV stroke volume index.86-89

Pulmonary Arterial Hypertension (Group 1)

The echocardiographic findings in idiopathic PAH are similar to those in patients with cor pulmonale. However, patients with group 1 PAH often have greater RVH and septal flattening (even concavity toward the LV), and this may precede inferior vena cava plethora.90 Doppler echocardiography can estimate the pulmonary artery systolic pressure, evaluate the right atrial and RV size and function, and evaluate the atrial and ventricular septum for cardiac shunting. Cardiac CT (direct) and nuclear ventilation-perfusion scan (indirect) can exclude the presence of significant pulmonary emboli.

The RIMP (Tei index) is an important risk-stratifying parameter in patients with PAH. The survival rate of patients with PAH and a Tei index ≥0.83 is worse after 1 year than in those with a Tei index <0.83.91 In a multivariate model, this was the only echocardiographic parameter that was an independent predictor of an adverse outcome.

Pericardial Constriction

The clinical presentation of patients with pericardial constriction may be similar to that of patients with an RV cardiomyopathy. Doppler echocardiography can be used for this assessment. Mitral, aortic, tricuspid valve flow; hepatic, pulmonary, and superior vein flow; and the respiratory variation provide the physiologic clues to this diagnosis.92 TDE has been found to have consistent and predictable findings in patients with pericardial constriction.93 The longitudinal velocity of the basal interventricular septum is increased and may exceed the normally higher basal LV lateral wall longitudinal velocity. This is thought to be due to a compensatory effect of the longitudinal myofibers in the setting of impaired circumferential and radial contraction from the constriction process. The reversal of the relation between the lateral and medial e′ velocities (ie, annulus reversus) is an important diagnostic clue to the presence of constriction. It is likely that this variable myofiber response to pathology occurs in other LV and RV settings but has yet to be identified. In addition to these Doppler-detected physiologic alterations that result from increased pericardial pressures, the pericardium can readily be visualized with CMR or CTA.

Arrhythmogenic RV Cardiomyopathy/Dysplasia

ARVC/D, clinically described nearly 30 years ago, represents the prototypical RV cardiomyopathy.54 It has been extensively studied and reported in a large international registry. In ARVC/D, the RV has an abnormal structure and function; in the late stage, there can be RV failure due to fibrofatty replacement of the RV myocardium with normal pulmonary pressures. Because 5 mm Hg is adequate to maintain a pressure difference from the RVOT to the pulmonary vasculature, right heart failure usually requires concomitant LV dysfunction (systolic or diastolic), loss of atrial function, or intermittent pulmonary pressure elevation (pulmonary emboli).94

There is no single specific diagnostic finding in patients with ARVC/D. Therefore, the diagnosis requires using a combination of clinical, ECG, genetic, and multimodal imaging findings. However, some morphologic features are consistently seen in patients meeting ARVC/D task force criteria.95

A normal FAC ≥32% was present in nearly all controls, and an FAC <32% was found in 65% of ARVC/D newly diagnosed probands but only 3% of controls.95 Additional markers of more subtle RV dysfunction can be used when the RV FAC is normal and include tissue Doppler imaging, TAPSE, and the RIMP (Fig. 19–19).96 Peak RV systolic velocity <7.5 cm/s and peak RV strain <18% were shown to best identify patients with phenotypically mild ARVC/D and an apparently normal RV.97

In an effort to quantify the RV size, Nava et al98 studied 132 patients with ARVC/D and categorized RV dilation having an end-diastolic volume of <75 mL/m2, 75 to 120 mL/m2, and >120 mL/m2 as mild, moderate, and severe, respectively (Fig. 19–20).98 These authors also noted patterns of regional RV dysfunction. Milder forms of the disease affect the RV apex. The RV inflow was impaired at all disease stages, and enlargement of the RVOT correlated with disease severity because it was dilated in 100% of those with severe disease, 50% of those with moderate disease, and only 29% of those mild disease. Others have shown the diagnostic importance of dilation of the RVOT. A cutoff value of 30 mm has a high sensitivity (89%) and specificity (86%) in correctly stratifying ARVC/D patients from controls (Fig. 19–21).

Because the hallmark of fibrofatty infiltration of the RV myocardium is regional dysfunction, careful assessment of tissue deformation using tissue Doppler imaging seems logical and was recently confirmed as a viable option for this purpose. In a small subset of 34 patients confirmed to have ARVC/D by task force criteria, a cutoff value of –18.2% had a 97% sensitivity and a 91% specificity for the diagnosis of this disease.99 The ability of this method to differentiate ARVC/D from other RV diseases has yet to be substantiated.

Despite the potential for CMR to be the reference standard for ARVC/D due to its ability to quantify RV size, evaluate global and regional function, and image fat (fat suppression sequence) and fibrosis (delayed contrast sequence), assessment of this disease entity remains a challenge. This is likely due to the variation of CMR image acquisition, the variable distribution and extent of fatty infiltration depending on disease severity, and the knowledge that some degree of fatty infiltration and regional outward systolic motion abnormalities are commonly seen in normal controls.100 Reliance on the finding of RV fat or subtle regional wall motion abnormality (especially near the moderator band and RV apex) may result in overdiagnosis of ARVC/D.101 In normal individuals, epicardial fat overlies the RV (often with a clear line of demarcation) and is most noted in the atrioventricular groove and near the apex. In patients with ARVC/D, the hyperintense fat signal extends through this line of demarcation indicating infiltration into the RV epicardium (usually in the RV inflow or outflow regions).102 To minimize the variability of image acquisition, standard CMR protocols have been published and deviations should be minimized.103

The presence of fibrosis in the RV is not normal and provides an important diagnostic clue to the presence of ARVC/D (Fig. 19–22). Delayed contrast enhancement with CMR correlates with histopathologic changes and regions of wall motion abnormalities, inversely correlates with RV global function, and predicts sustained ventricular tachycardia during electrophysiologic testing.104 CMR provides an excellent method for the assessment of ARVC/D when there is a high-quality, expertly interpreted examination. If the CMR is completely normal, it may eliminate the need for subsequent invasive testing.

CT imaging in ARVC/D is usually reserved for patients with contraindications to CMR. The advantages of CT are quick scan time, minimal operator dependence, and consistent image quality, and it can be used in patients with pacemakers and implantable cardioverter-defibrillator devices. Attenuation of intramyocardial fat (5 to –17 Hounsfield units; HU) is significantly less than attenuation of normal myocardium (73 ± 14 HU) and greater than epicardial fat (–65 ± 10 HU) (Fig. 19–23).105 Another advantage of CT is excellent visualization of the mediastinum to assess for lymphadenopathy, a marker of sarcoidosis, which is known to mimic ARVC/D.106 Disadvantages include low temporal resolution and registration artifacts limiting wall motion assessment, image deterioration from lead artifacts, and the requirement for retrospective gating, which increases radiation exposure making this procedure less optimal for the young or for serial investigations.

Angiography remains a reference imaging standard of the RV for the diagnosis of ARVC/D. The well-known regions of abnormal function, termed the "triangle of dysplasia," consisting of the RVOT, apex, and subtricuspid valve regions, can be examined in multiple angiographic views for hypokinesis, akinesis, or dyskinesis (aneurysmal segments). In addition to wall motion abnormalities, angiography can delineate other abnormalities, such as prolonged persistence of dye in aneurysmal segments.107 Angiography may also reveal a polycyclic contour, or cauliflower-like appearance, a specific but nonsensitive finding for ARVC/D, because this occurs in advanced stages of the disease. Thick trabeculation (>4 mm) with deep horizontal fissuring, referred to as "pile d'assiettes," is characteristic in ARVC/D, particularly if it involves the moderator band, the papillary muscles, and the apex and superior-apical region.108 Nonetheless, marked trabeculation can also occur in normal subjects and needs to be evaluated in conjunction with other RV abnormalities.

In a cohort of ARVC/D patients, wall motion was decreased by more than 30% at the tricuspid valve region and by 50% in the subtricuspid region compared to normal individuals.109 Furthermore, a poor TAPSE excursion correlated with decreased RVEF.110 However, because there is minimal contraction of the RVOT and anterior wall in normal subjects, the wall motion in these regions is not significantly different in ARVC/D patients.

The fact that ARVC/D is rare only compounds the difficulty of diagnosing it. Combining a rare disease with the difficulty in interpretation of the irregular shaped RV leads to over- and underdiagnosis of ARVC/D.101 When the imaging abnormality is documented by at least two imaging modalities, it increases the accuracy of the finding. If present on only one imaging test, RV angiography should be considered, or the tests should be referred to experts for re-evaluation. In 89 patients with an initial diagnosis of ARVC/D (34% who received an implantable cardioverter-defibrillator device) who were sent for expert re-evaluation, only 24 (27%) met task force criteria for ARVC/D. Importantly, none of the 46 patients diagnosed solely by CMR criteria of wall thinning and RV myocardial fat fulfilled ARVC/D criteria.111

UHL Anomaly

This unusual RV cardiomyopathy is typified by an extremely thin ("paper-thin") RV wall with essentially endocardial apposition to the epicardium, sparing the normal mid-myocardial layer. If the majority of the RV is involved, ineffective RV contraction results in the RV acting as a conduit for blood, rather than a pumping chamber. Lack of myocardial contraction should be recognized with any diagnostic tool capable of critically evaluating myocardial segments. Lack of RV contraction results in compensatory hyperdynamic septal contraction and hypertrophied RA wall. Although displaying many characteristics of ARVC/D, this anomaly is rarely seen in adults, has not been found to be congenital, and does not have significant fatty replacement.112

With modern echocardiographic imaging probes, one can see a well-defined separation of the interventricular septum into RV and LV myofibers.113 It is not known if this feature will eventually improve our understanding of RV performance and, specifically, how the interventricular septum influences the RV. This warrants additional investigation.

One particularly interesting imaging technique with direct application to ARVC/D is radiolabeled 123I-mIBG, also known as iobenguane, an analog of the false neurotransmitter guanethidine. Japanese investigators have demonstrated LV myocardial 123I-mIBG defects in ARVC/D patients that correspond to regions of CCT and CMR fatty infiltration.114 None of these patients had ventricular tachycardia originating from the LV on electrophysiologic testing. It was previously shown that 123I-mIBG LV defects commonly localize in the ventricular septum and regions contiguous to the RV.115 These regions are anatomically and sympathetically related. A subepicardial, primarily RV, dysplastic cardiomyopathy would likely impair the LV in this region early in its disease progression. Further investigation is required to fully evaluate the potential of advanced radiopharmaceuticals for the investigation of these patients. It is likely that additional specific molecular agents will become available and provide incremental diagnostic and managerial roles in this and other rare cardiomyopathies.

Multigated RNA is still considered the reference standard for ventricular volume and function assessment, although CMR has become more accurate and does not expose the patient to irradiation. Time-volume activity curves generated with RNA can accurately assess global and regional RV motion with adequate temporal resolution. Using offline software and novel processing techniques to reduce noise and focusing on regions of dyskinesia, this method effectively distinguishes normal controls from ARVC/D patients with regional or diffuse hypokinesia.116 Nonetheless, it is not specific for ARVC/D, but rather demonstrates any RV pathologic, dyssynchronous motion. It is not known whether this will provide incremental value to the previously listed alternative techniques.

Genetic markers aimed at reclassifying specific cardiomyopathies and assisting in treatment development are rapidly being identified. For example, ARVC/D shows autosomal dominant inheritance and has been mapped to eight chromosomal loci, with mutations identified thus far in seven genes. One gene mutation shares an arrhythmic profile with familial catecholaminergic polymorphic ventricular tachycardia. Furthermore, two recessive forms are caused by mutations in junctional plakoglobin (Naxos disease) and desmoplakin (Carvajal syndrome).117 A link with ion channel disorders (channelopathies) has been described beyond the primary structural pathologic findings. Given the subtlety of early morphologic changes in this disease and the inherent difficulties in evaluating early RV impairment from any pathology, the ability to detect genotypic impairment will influence the future assessment of phenotypic expression using multimodal imaging.