MRI in the Diagnosis of Right Ventricular Dysplasia M. M

M. M

, M. G

, T.V. B

Introduction

Arrhythmogenic right ventricular dysplasia (ARVD) is a form of cardiomy- opathy that is characterised clinically by ventricular arrhythmias with left bundle branch block (LBBB) that may lead to cardiac arrest and morpholog- ically by fatty or fibrofatty infiltration of the right ventricular myocardium [1–5]. Although the incidence and prevalence of ARVD are unknown, ARVD is recognised as a major cause of sudden death in young adolescents; in one series it accounted for 20% of sudden deaths in all individuals younger than 35 years and 22% of sudden deaths in young athletes [6]. Therefore, an early and accurate diagnosis followed by appropriate therapy for this condition is increasingly important, for it may prevent lethal arrhythmias.

Aetiology

ARVD must be considered as a part of the group of idiopathic cardiomy- opathies, based on its nature of progressive heart muscle disease with unclear pathogenesis and aetiology. The male-to-female ratio is 2.7:1.0.

Basso et al. [1] addressed the aetiology and pathogenesis and proposed four hypotheses as possible explanations. The first hypothesis concerns apoptosis, that is, programmed cell death, which leads to progressive myocar- dial muscle loss followed by fibrofatty replacement and enhances the electri- cal vulnerability of the right ventricle, which in turn can cause potentially life-threatening arrhythmias [7]. According to the dysontogenetic theory, ARVD should be regarded as a congenital heart disease in which abnormal

Dipartimento di Biotecnologie Mediche e Medicina Legale, Sezione di Scienze

Radiologiche, University of Palermo, Italy

development of the right ventricle may lead to dysplasia. In the degenerative theory, a metabolic disorder may affect the right ventricle and result in pro- gressive replacement of myocardial cells by fat and fibrous tissue. In the inflammatory theory, the fibrofatty replacement is viewed as a healing process in the context of myocarditis [8].

Several reports suggest that there is a familial occurrence of ARVD of about 30–50% [2, 9–12], with mainly autosomal dominant inheritance, vari- able penetrance, and polymorphic phenotypic expression. Several genetic disorders responsible for ARVD have been identified on chromosome 14 and, recently, on chromosome 3 [9, 11, 12]. The diagnosis of ARVD may have important consequences for direct relatives, because they have an increased chance of having the disease, and therefore an increased risk of sudden death. Gene mapping may open new avenues for cloning the defective gene, identifying the encoded protein, and potentially instituting gene therapy.

Four loci have been mapped, but none of the genes have been identified yet, and the findings of polymorphism in ARVD currently preclude gene therapy [5, 9, 11].

Pathological Features

Two morphological variants of ARVD have been reported: fatty and fibrofat- ty [6, 13–16]. The fatty form is characterised by almost complete replacement of the myocardium without thinning of the ventricular wall, and it occurs exclusively in the right ventricle. The fibrofatty variant is associated with sig- nificant thinning of the right ventricular wall, and the left ventricular myocardial wall may also be involved. Other anatomic malformations of the right ventricle associated with ARVD consist of mild to severe global dilata- tion of the ventricle, ventricular aneurysms, and segmental hypokinesia. The sites of involvement of anatomic abnormalities are found in the so-called tri- angle of dysplasia, namely, the right ventricular subtricuspid areas, the apex, and the infundibulum [14].

Clinical Characteristics

The clinical manifestations of ARVD may vary widely, but the disorder is

classically characterised by ventricular tachycardia with LBBB, originating

from the right ventricle. ARVD probably represents a spectrum of different

abnormalities rather than a single identity, and ranges from an asympto-

matic form consisting of ventricular ectopic beats to biventricular heart fail-

ure with or without arrhythmias and sudden death in young patients and

athletes [5, 15]. Furthermore, ARVD is a disease that may have a temporal progression, and the disease may manifest differently according to the time of patient presentation.

Prognosis and Therapy

Although the prognosis of ARVD is considerably better than that of sus- tained ventricular tachycardia with left ventricular heart disease, ARVD is a progressive disease and will probably lead to right ventricular failure in the long term unless sudden cardiac death occurs first. The death rate for patients with ARVD has been estimated at 2.5% per year [17]. The disease certainly cannot be considered as a benign condition in patients with symp- toms of syncope, episodes of recurrent ventricular tachycardia, and anatomic or functional abnormalities of the right ventricle [18].

Fortunately, patients with recurrences of ventricular tachycardia have a favourable outcome when they are treated medically. The four therapeutic options in patients with ARVD are antiarrhythmic agents, catheter ablation, implantable cardioverter defibrillators, and surgery [19]. Pharmacological treatment is the first choice, the antiarrhythmic agents being sotalol, vera- pamil, beta-receptor-blocking agents, amiodarone, and flecainide. Catheter ablation is an alternative in patients who do not respond to drug treatment and who have localised disease. In addition, catheter ablation has been shown to improve the effectiveness of pharmacological treatment: 70% of patients may respond to antiarrhythmic agents to which they were unre- sponsive prior to ablation therapy [20]. Implantation of cardioverter defibril- lators is indicated in patients who are intolerant of antiarrhythmic therapy and who are at serious risk of sudden death. Surgery should be considered only as a very last resort, and treatment consists initially of ventriculotomy, followed by total disconnection of the right ventricular free wall. In the case of progressive or intractable right ventricular failure, cardiac transplantation may be the ultimate option for treating patients with ARVD. Currently, drug treatment, ablation, and cardioverter defibrillator therapy are the most suit- able therapeutic approaches in patients with ARVD.

MR Imaging Assessment

ARVD is being diagnosed with increasing frequency, mostly because MR

imaging allows improved recognition of myocardial fatty and fibrofatty

replacement [13]. Several studies have reported on the use of MR imaging to

detect the characteristic high signal intensity of fat in the right ventricular

myocardium on T

-weighted images [1, 6, 21–24]. However recent studies demonstrated that significant fatty infiltration of the right ventricle occurs in more than 50% of normal hearts in elderly people [25, 26]. Mehta et al.

[27] found signs of fatty replacement in only 22% of 27 patients with ventric- ular tachycardia with LBBB (as diagnosed with endomyocardial biopsy).

Menghetti et al. [21] reported a sensitivity and specificity of 67% and 100%, respectively, with the use of spin echo MR imaging. Basso et al. [1], however, found that among nine patients with the pathological diagnosis of ARVD (based on gross or histological evidence of regional or diffuse transmural fatty or fibrofatty replacement), MR imaging revealed abnormally high sig- nal intensity in all cases [1]. Although these findings indicate that the pres- ence of some fat in the right ventricular myocardium may not be specific enough for the diagnosis of ARVD, the presence of transmural fatty replace- ment or diffuse thinning of the right ventricular myocardium as demonstrat- ed with MR imaging should be considered in the overall clinical context to be a major criterion for the diagnosis of ARVD.

Several studies examined the value of using MR imaging in patients for whom the first manifestation of right ventricular disease was right ventricu- lar outflow tract tachycardia [28–34]. Carlson et al. [30] showed that right ventricular outflow tract tachycardia was associated with local structural and wall motion abnormalities of the right ventricular outflow tract, and that the structural abnormalities observed with MR imaging were often not detected with echocardiography. Proclemer et al. [34] investigated 19 patients who had frequent ventricular extrasystoles (100/h) with LBBB pat- tern (minor criterion). In all 19 patients, results from two-dimensional echocardiography were normal; however, MR imaging showed significantly greater dimensions of the right ventricular outflow tract than those seen in the control group of 10 volunteers. The similarity of these findings to those previously obtained in patients with right ventricular tachycardia suggests a similar underlying mechanism of the right ventricular outflow tract arrhyth- mias.

MR imaging can also be used to assess both systolic and diastolic func-

tion in great detail. Several studies have addressed the presence of right ven-

tricular diastolic dysfunction as an early marker of disease, even when sys-

tolic function is still preserved [35]. In a previous study, we showed that

diastolic function of the right ventricle was significantly altered in 15

patients with non-ischaemic tachyarrhythmias of right ventricular origin,

even though systolic function was normal [31]. Of the 15 patients in that

study, 5 (33%) had a clinical diagnosis of ARVD, indicating that ARVD may

be associated with diastolic function abnormalities preceding systolic func-

tion abnormalities. Therefore, it could be suggested that diastolic dysfunc-

tion might be considered as an additional feature or criterion of ARVD. The

typical criteria that can be demonstrated with MR imaging are (a) fatty infil- tration of the right ventricular myocardium with high signal intensity on T

- weighted images (major criterion); (b) fibrofatty replacement, which leads to diffuse thinning of the right ventricular myocardium (major criterion); (c) aneurysms of the right ventricle and right ventricular outflow tract (major criterion); (d) dilatation of the right ventricle and right ventricular outflow tract (when severe, major criterion; when mild, minor criterion); (e) regional contraction abnormalities (minor criterion); and (f) global systolic dysfunc- tion (major criterion) and global diastolic dysfunction (minor criterion).

In summary, MR imaging is useful for evaluating not only fatty replace- ment of the right ventricular myocardium, but also global and regional func- tional abnormalities of the right ventricle and right ventricular outflow tract. The demonstration of right ventricular abnormalities should be con- sidered in the overall clinical context.

MR Imaging Protocol

For all examinations, a phased array cardiac synergy coil with five elements has to be used. For the evaluation of right ventricular anatomy, we perform a multisection inversion-recovery (‘black blood’) segmented turbo spin echo pulse sequence to obtain images with section thicknesses of 4 mm or less in transverse and sagittal planes. ‘Black blood’ in MR images can be achieved by using a non-selective 180° pulse to invert all spins. This inversion pulse is directly followed by a selective 180° pulse, which resets the signal of the sec- tion under investigation. This technique causes the blood with inverted sig- nal to flow into the selected section. After a delay (inversion time), the blood signal is nulled (inversion time depends on heart rate) and the imaging pulse sequence (e.g. a fast spin echo during patient breath-hold) is started [36, 37].

For the evaluation of right ventricular global and regional systolic function, we use a multisection, multiphase, balanced fast-field-echo pulse sequence [38] to obtain images with section thicknesses of 8–9 mm in the transverse plane. Balanced fast-field-echo pulse sequences belong to the group of

‘steady state free precession’ sequences and are characterised by the applica- tion of time-balanced gradients for all gradient directions: section selection, frequency readout, and phase encoding. Together with the alternating phase of the excitation pulse, this technique ensures that both signals (free induc- tion decay and echo) are obtained. The sequence produces a very high signal for tissues with a high T

:T

ratio, independent of the repetition time. The balanced gradients contribute to a low sensitivity for flow disturbances.

Because the field homogeneity is very important, balanced fast field echo

requires the use of shimming before each study. For the evaluation of right

ventricular diastolic function, MR velocity mapping is performed to measure flow across the tricuspid valve [39]. The number of time frames used to sam- ple the cardiac cycle is set to 30, resulting in a temporal resolution of less than 30 ms per cardiac frame. Peak velocity is set at 100 cm/s to avoid alias- ing. Flow measurements are performed in double oblique planes, identified from a coronal spin echo image and a transverse gradient echo image. End- diastolic and end-systolic positions of the tricuspid valve are determined, and the imaging plane is selected between these positions perpendicular to transtricuspid flow direction.

Summary

ARVD is part of the group of cardiomyopathies characterised pathologically by fibrofatty replacement of the right ventricular myocardium and clinically by right ventricular arrhythmias of the LBBB pattern. Pathogenesis, preva- lence, and aetiology are yet not fully known. The diagnosis of ARVD is based on the presence of structural, histological, electrocardiographic, and genetic factors. Therapeutic options include antiarrhythmic medication, catheter ablation, implantable cardioverter defibrillation, and surgery. Angiography and echocardiography lack sensitivity and specificity in the diagnosis of ARVD. MR imaging allows a three-dimensional evaluation of especially the right ventricle, and provides the most important anatomical, functional, and morphological criteria for diagnosis of ARVD within one single study.

Although demonstration of morphological/functional abnormalities of the right ventricle, especially fat in the right ventricular myocardium, shows high specificity but low sensitivity, MR imaging appears to be the optimal imaging technique for detection and follow-up of clinically suspected ARVD.

Positive MR imaging findings, based on the criteria of McKenna et al. [16], should be used as important additional criteria in the clinical diagnosis of ARVD, although negative MR imaging findings do not rule out ARVD.

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