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(Circulation. 1997;96:1192-1200.)
© 1997 American Heart Association, Inc.

Articles

Adenosine-Sensitive Ventricular Tachycardia

Right Ventricular Abnormalities Delineated by Magnetic Resonance Imaging

Steven M. Markowitz, MD; Bonnie L. Litvak, MD; Elizabeth A. Ramirez de Arellano, MD; John A. Markisz, MD, PhD; Kenneth M. Stein, MD; ; Bruce B. Lerman, MD

From the Department of Medicine, Division of Cardiology, and the Department of Radiology, The New York Hospital–Cornell University Medical Center, New York, NY.

Correspondence to Bruce B. Lerman, MD, Division of Cardiology, Starr 4, The New York Hospital–Cornell Medical Center, 525 E 68th St, New York, NY 10021. E-mail blerman{at}mail.med.cornell.edu

	Abstract

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Background Adenosine-sensitive ventricular tachycardia (VT) is thought to be due to cAMP-mediated triggered activity. It typically originates from the RVOT and occurs in patients with apparently normal hearts. Using magnetic resonance imaging (MRI), we tested the hypothesis that adenosine-sensitive VT occurs in patients without structural heart disease.

Methods and Results Fourteen patients (9 women; age, 47±19 years) presented with sustained VT (n=3), repetitive monomorphic VT (n=7), or both (n=4). VT terminated with adenosine in each patient and was sensitive to vagal maneuvers in 9 of 11 and verapamil in 10 of 12. VT originated from the right ventricular outflow tract in 10 patients, the right ventricular apex in 1, and the left ventricular septum in 3. Conventional studies included normal signal-averaged ECGs in 9 of 9, normal right ventricular echocardiography in 10 of 10, and normal left ventriculography and coronary angiography in 6 of 7. In contrast, MRI scans were abnormal in 10 of 14 patients. These abnormalities included focal thinning (6), fatty infiltration (4), and wall motion abnormalities (4) of the right ventricle. The most common site of MRI abnormalities was the right ventricular free wall, but there was a poor correlation between the site of MRI abnormalities and the origin of VT. Among 18 control patients without clinical heart disease, thinning of the right ventricular wall was noted in only 1 patient (patients versus control subjects, P=.0001).

Conclusions Patients with idiopathic adenosine-sensitive VT comprise a heterogeneous group as assessed by MRI, with 70% demonstrating mild structural abnormalities. However, it is unlikely that these findings are causally related to tachycardia, and the functional significance of these anatomic abnormalities is uncertain.

Key Words: imaging • tachycardia • ventricles

	Introduction

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Idiopathic VT is defined as a ventricular arrhythmia that occurs in the absence of structural heart disease and is thought to be a "primary electrical disease." This characterization has relied on conventional imaging and diagnostic modalities, such as echocardiography, exercise stress testing, and coronary angiography.^{1 2 3 4 5 6 7} Subsequent analyses of patients with VT in the absence of clinically evident heart disease have used endomyocardial biopsy, signal-averaged ECG, and MRI to define previously undetected abnormalities.^{3 8 9 10 11 12 13 14 15 16 17 18 19} These reports have yielded conflicting results due to the heterogeneous nature of the populations studied with respect to the mechanisms of arrhythmogenesis.

The most common form of idiopathic VT originates from the RVOT and is associated with an LBBB, inferior axis morphology.^{1 4 7 10 12 13 14 15 20 21 22 23 24} Although multiple mechanisms may be responsible for tachycardia originating in this region, including reentry and automaticity, the most common and completely described subtypes are due to triggered activity arising from delayed afterdepolarizations, which are dependent on cAMP and intracellular calcium overload.^{20 21 22 25} These subtypes of idiopathic VT include exercise or stress-induced sustained VT and nonsustained RMVT. These forms of VT are facilitated by catecholamines and characteristically terminate with adenosine as well as vagal maneuvers, ß-blockers, and verapamil.

The primary defect in adenosine-sensitive VT has not been defined. Potential defects may reside at the molecular and cellular level (ie, in the ß-adrenergic signal transduction cascade) or at the level of myocardial innervation (ie, denervation hypersensitivity). Alternatively, the arrhythmia may be due to a subtle structural abnormality in the RV. Echocardiography and cardiac catheterization have limited sensitivity in detecting abnormalities in RV structure and function, and MRI with cine wall motion analysis has emerged as a more sensitive modality for imaging the RV.¹⁸ In this study, we used MRI to screen a homogeneous population of patients with idiopathic adenosine-sensitive VT for abnormalities in RV structure and function.

	Methods

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Patient Population
Patients and a control study group were enrolled in a protocol approved by the Institutional Review Board at the New York Hospital–Cornell Medical Center. The study population consisted of 14 patients with adenosine-sensitive VT (9 women; mean age at the time of presentation, 47±19 years; age range, 6 to 75 years). Clinical characteristics of patients are presented in Table 1. Three patients presented with paroxysmal sustained VT and 11 presented with RMVT, four of whom also had at least one documented episode of sustained VT. Patients with RMVT were characterized by frequent ventricular extrasystoles, ventricular couplets, and recurrent runs of nonsustained VT (3 to 30 beats) with intervening sinus rhythm. The presenting symptoms were palpitations (12), presyncope or syncope (7), and chest pain (3); one patient was asymptomatic. The duration of symptoms was 58±131 months before the index electrophysiological study. Eight of these patients have been previously described (patients 2, 4 to 7, and 9 to 11) in a series of patients with RMVT.²² The control population consisted of 18 age- and sex-matched volunteers (12 women; mean age, 46±16 years; age range, 6 to 59 years) with no clinical history of heart disease as assessed by questionnaire.

View this table: [in this window] [in a new window]   Table 1. Clinical Characteristics of Patients With Adenosine-Sensitive VT

Electrophysiological Study and Ablation Protocol
Electrophysiological studies were performed after discontinuation of all antiarrhythmic agents for at least five half-lives. Three quadripolar electrode catheters were inserted percutaneously and advanced under fluoroscopic guidance to the high right atrium, RV apex, and AV junction for recording of the His bundle electrogram. In addition, a quadripolar mapping catheter was introduced into the RV or left ventricle after induction of VT. Bipolar intracardiac recordings were filtered at 30 to 500 Hz and displayed simultaneously with three surface ECG leads on a multichannel oscilloscope or digital monitor. Data were stored on magnetic tape or optical disk (Prucka Engineering). Systemic arterial pressure was continuously monitored (Dinamap, Critikon). Stimulation was performed with a programmable stimulator and an isolated constant current source (Bloom Associates), and stimuli were delivered as rectangular pulses of 2-ms duration at four times diastolic threshold. The stimulation protocol included the introduction of single, double, and triple extrastimuli during several paced cycle lengths and rapid burst pacing from multiple atrial and ventricular sites. In addition, the ability of isoproterenol (2 to 10 µg/min) to initiate VT either alone or during concurrent pacing was evaluated.

Inclusion in this study required that patients have inducible sustained VT at electrophysiological study that terminated with adenosine (100 to 475 µg/kg IV) given as a rapid bolus followed by a saline flush or incessant nonsustained monomorphic VT that was suppressed with a comparable dose of adenosine. In addition, the following pharmacological sensitivities were tested: (1) edrophonium, given as a 1-mg IV test dose followed by 9 mg IV over 1 minute, (2) esmolol, one or two boluses of 500 µg/kg IV over 1 min followed by an infusion of 50 to 100 µg/kg/min; or 0.1 mg/kg propranolol IV over 5 minutes, and (3) 10 to 15 mg verapamil IV infused over 1 minute. Vagal maneuvers such as Valsalva and carotid sinus massage were also evaluated. Sensitivity of nonsustained VT to these pharmacological interventions was defined as the absence of ventricular ectopy for a specified time after intervention, with recurrent ventricular couplets and runs of nonsustained VT in the 60 seconds preceding a perturbation. In the cases of adenosine and vagal maneuvers, suppression of ectopy was required for 10 seconds after intervention. Comparable times were 1 minute after administration of edrophonium and 5 minutes after infusion of verapamil. Noninducibility of VT by programmed stimulation after administration of verapamil was also regarded as evidence for suppression if VT was reproducibly induced before intervention.

Detailed activation and pace mapping were performed in 12 patients to identify the focal origin of VT and guide ablation. An adequate pace map was defined as a match of 11 or 12 surface leads during pacing at the tachycardia cycle length. If an adequate pace map was not obtained in the RV, pace mapping was performed in the left ventricular outflow tract via a retrograde approach. In the remaining 2 patients, the origin of VT was inferred from the morphology of VT on the surface ECG.

Radiofrequency ablation was performed in 11 patients with current generated by a conventional 500-kHz radiofrequency energy source (EPT-1000, EP Technologies or Radionics) delivered from the 4-mm tip of a steerable mapping catheter (EPT Steerocath-T, EP Technologies or Mansfield EP) to a left subscapular chest wall patch (7.25x1.5 in). Energy was applied at 10 to 50 W for 60 seconds to obtain a tip temperature of 60° (where monitored) or until an abrupt rise occurred in catheter impedance. DC ablation was performed in 1 patient. After positioning of the mapping catheter (6F quadripolar, Bard Electrophysiology) at the site of an appropriate pace map, two DC shocks of 200 J each were delivered via a conventional defibrillator (Zoll) to a subscapular patch. Successful ablation was defined by the absence of spontaneous and inducible VT 30 minutes after the procedure.

Signal-Averaged ECG
Signal averaging was performed using standard bipolar X, Y, and Z leads and a high-pass filter of 40 Hz (Predictor, Corazonix Inc). Beats were averaged to obtain a noise level of 0.3 µV. The filtered QRS vector was analyzed for QRS duration (normal <114 ms), RMS voltage of the terminal 40 ms of the QRS (normal >20 µV), and the duration of the LAS <40 µV (normal <38 ms). The signal-averaged ECG was regarded as abnormal if the filtered QRS duration was prolonged and terminal RMS voltage, LAS duration, or both were abnormal.

MRI
All patients and control subjects underwent an identical MRI protocol. The MRI imaging study was conducted a mean of 26±22 months after the initial electrophysiological study. In patients who underwent ablation, MRI was performed a mean of 21±16 months (range, 1 day to 58 months) after ablation; in 1 patient, MRI was performed 1 day before electrophysiological study and ablation. In the 2 patients who did not have ablation, MRI was performed 19 and 57 months after the initial electrophysiological study.

MRI studies were performed on a General Electric Signa 1.5-T system. All scans were regular spin echo sequences, which were gated to the R wave of the ECG. Respiratory compensation was also applied to minimize breathing artifact. The following sequences were used to obtain static images: T1-weighted coronal, T1-weighted axial, T2-weighted axial, and T1-weighted axial with a saturation pulse placed posterior to the interventricular septum. The repetition time (TR) was determined by the RR interval, and the echo time (TE) was 20 ms. Slice thickness was 5.0 mm with an interslice spacing of 1.5 mm. Data were collected using a 256x128 matrix with two data acquisitions and a field of view of 32 to 40 cm depending on patient size and habitus.

Cine images were obtained using cardiac-gated gradient echo pulse sequences with flow compensation to increase the contrast of flowing blood. Contiguous 10-mm axial sections were obtained from above the pulmonary artery to below the diaphragmatic walls of the heart. For each axial section, 16 frames were obtained, equally spaced within the RR interval. Each set of images for a given axial section was played sequentially in a cine mode to visualize wall motion and flow abnormalities. In two subjects (patient 13 and a 6-year-old male control subject), cine images were not obtained due to inability to tolerate the complete protocol, and the evaluation was limited to static images.

Each study was separately interpreted by three radiologists who were blinded to the patient's clinical status and examined for abnormalities of the morphology of the RV free wall, RVOT, and left ventricle. High-intensity lesions on T1-weighted images were interpreted as fatty deposition. Fatty infiltration was defined only if the observed abnormality was intramyocardial; signal intensity from the region of fatty infiltration was compared with neighboring subepicardial muscle, and an abnormality was defined only if intervening epicardial tissue was devoid of fat. Contiguous slices were examined to confirm that tissue surrounding the deposit was free of fatty infiltration. Measurements of RV wall thickness were performed on spin echo images obtained during systole. Images were synchronized with R wave of the ECG with a delay of 150 ms; all images from the region of the heart were obtained within 80 ms of the earliest slice. Measurements of wall thickness refer to the anterior RV free wall, which is defined as the wall between the RV apex and the tricuspid annulus, as imaged in axial sections. Focal thinning of the RV free wall was defined as a wall thickness of <2 mm, with the abnormal region thinner than neighboring segments. Cine studies were evaluated separately from the static images and studied for irregularities in wall motion and wall thickening in each of the chambers, as well as irregular blood flow patterns. Focal hypokinesis and dyskinesis were defined, respectively, as decreased systolic excursion and paradoxical motion of an RV wall segment compared with neighboring segments, as assessed visually. Abnormalities were defined if observed by two of the three observers.

Statistical Analysis
Results are presented as mean±SD where appropriate. Comparisons between groups were performed with the Fisher exact test, the two-tailed t test for independent groups, and the Mann-Whitney test for nonparametric variables. A value of P<.05 was required to reject the null hypothesis.

	Results

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Electrophysiological Findings
At electrophysiological study, a single morphology of VT was induced in 13 patients, demonstrating an LBBB morphology in 11 (inferior axis in 10, superior axis in 1) and an RBBB morphology in 2 (inferior axis in 1, superior axis in 1). In 1 patient (patient 2), two morphologies of VT were induced: LBBB, inferior axis; and RBBB, inferior axis with identical cycle lengths.

VT could be induced with programmed stimulation in 12 patients and was present incessantly in 2 patients. Sustained VT (>30 beats) was induced in 11 patients, and adenosine reproducibly terminated sustained VT in each patient (Fig 1). Repetitive runs of nonsustained VT were present in the remaining 3 patients and could be induced with programmed stimulation in 1; adenosine suppressed ventricular ectopy in each of these patients. Facilitation of VT induction with isoproterenol was demonstrated in 12 patients. VT terminated with vagal maneuvers or edrophonium in 9 of 11 patients, and the arrhythmia terminated or was rendered noninducible after administration of verapamil in 10 of 12 patients (Table 2).

View larger version (7K): [in this window] [in a new window]   Figure 1. Termination of VT with adenosine. Surface leads I, aVF, V1, and an intracardiac electrogram from the RV apex (RVA) are shown from patient 14.

View this table: [in this window] [in a new window]   Table 2. Electrophysiological Results

VT originated from the RVOT in 10 patients, the RV apex in 1, and the left ventricular septum in 3. Of 10 patients with an LBBB, inferior axis VT morphology, pace mapping localized the arrhythmogenic focus to the RV outflow tract in 7. In 1 patient demonstrating VT with an LBBB, inferior axis morphology (patient 11), adequate pace maps were obtained in the RVOT, and radiofrequency ablation was performed in this region. After the recurrence of tachycardia with a similar morphology 1 year later, pace mapping localized the tachycardia to the left ventricular septum, where successful ablation was performed (Figs 2 and 3). Two patients with an LBBB, inferior axis morphology, did not undergo detailed mapping, and the site of origin was inferred to be the RVOT (patients 3 and 9). In the 1 patient demonstrating VT with an LBBB, superior axis, an exact pace map was obtained at the RV apex. In the 2 patients demonstrating VT with an RBBB, pace mapping localized the arrhythmogenic foci to the superior septal region of the left ventricle.

View larger version (10K): [in this window] [in a new window]   Figure 2. Localization of VT induced at electrophysiological study in patient 11. The 12-lead ECG (left) demonstrates VT with an LBBB, inferior axis morphology. The pace map (right) was obtained from the LVOT at the site depicted in Fig 3.

View larger version (144K): [in this window] [in a new window]   Figure 3. Anteroposterior fluoroscopic image from patient 11 indicating the position of the mapping catheter in the LVOT. The pace map from this site is presented in Fig 2. HB indicates His bundle.

Radiofrequency ablation was performed in 11 patients (mean, 14±8 applications of radiofrequency energy), and DC ablation was performed in 1 patient (patient 2). The 2 patients not undergoing ablation have been maintained on verapamil with clinical improvement.

Conventional Assessment for Structural Heart Disease
Surface ECGs were normal in 12 patients. One patient demonstrated left ventricular hypertrophy (patient 1), and one demonstrated an RV conduction delay (patient 6). Signal-averaged ECGs demonstrated no evidence for late potentials in 9 of 9 patients. Echocardiography demonstrated normal RV architecture in 10 of 10 patients; mild left-sided valvular abnormalities (mitral valve prolapse, mild mitral and aortic regurgitation) were noted in 4 patients. Left ventriculography and coronary angiography were normal in 6 of 7; 1 patient demonstrated a moderate (50%) stenosis of the mid left anterior descending coronary artery.

In 1 patient who presented with repetitive monomorphic VT demonstrating an LBBB, left inferior axis morphology (patient 6), considerable lability was evident on the surface ECG during sinus rhythm. On presentation, an RV conduction delay with normal anterolateral T waves was present (Fig 4A); 3 days later, anterolateral T-wave inversions were evident (Fig 4B). A treadmill test was normal (96% maximal predicted heart rate), and echocardiography was normal. Pace mapping identified the arrhythmogenic focus in the RVOT (Fig 5), and successful ablation was performed at this site (Fig 6).

View larger version (14K): [in this window] [in a new window]   Figure 4. Twelve-lead ECGs from patient 6. A, At presentation, an RV conduction delay with normal anterior T waves was present. B, Three days later, anterior T-wave inversions, in addition to the RV conduction delay, were evident.

View larger version (62K): [in this window] [in a new window]   Figure 5. Fluoroscopic images from patient 6 indicating the site of successful radiofrequency ablation in the RVOT. A rhythm strip during ablation from this site is presented in Fig 6. ABL indicates ablation catheter; RVA, RV apex.

View larger version (16K): [in this window] [in a new window]   Figure 6. Rhythm strip and intracardiac electrogram during radiofrequency ablation of repetitive monomorphic VT in patient 6. The mapping catheter was positioned in the RVOT as demonstrated in Fig 5. Surface leads II and aVF and an intracardiac electrogram from the RV apex (RVA) are shown.

MRI
MRI scans in 17 of 18 control subjects demonstrated no abnormalities of ventricular structure or function. In 1 control 6-year-old boy, the MRI demonstrated mild thinning of the RV free wall on static spin echo images, but no wall motion abnormalities were detected on cine images. In contrast, 10 of 14 patients with adenosine-sensitive VT demonstrated an abnormality by MRI (patients versus control subjects, 71% versus 6%, P=.0001). Six patients demonstrated focal thinning of the RV free wall, defined as a localized region with wall thickness of <2 mm. In contrast, RV wall thickness exceeded 2 mm in 17 control subjects. Fatty infiltration of the RV wall was demonstrated in 4 patients with VT, and wall motion abnormalities of the RV were present in 4 (Table 3 and Figs 7 to 9). These abnormalities were not present in control subjects. Left ventricular hypertrophy and hypokinesis of the left ventricular apex were each noted in 2 patients.

View this table: [in this window] [in a new window]   Table 3. MRI Results

View larger version (142K): [in this window] [in a new window]   Figure 7. Normal MRI scan. This T1-weighted axial section from patient 4 demonstrates normal ventricular anatomy. LV indicates left ventricle; RA, right atrium.

View larger version (117K): [in this window] [in a new window]   Figure 8. MRI scan demonstrating thinning of the RV wall. This T1-weighted axial image from patient 2 demonstrates extreme thinning of the anterior RV free wall. On the cine loop, decreased systolic thickening was present in the RV free wall. HB indicates His bundle.

View larger version (118K): [in this window] [in a new window]   Figure 9. MRI scan demonstrating fatty infiltration of the RV wall. This T1-weighted axial image from patient 6 demonstrates fat deposition within the RV free wall (arrow). On the cine loop, decreased systolic thickening was present in this region. Note the normal distribution of fat in the AV groove and epicardium. Left ventricular hypertrophy is also present. HB indicates His bundle; LVOT, left ventricular outflow tract.

The most common site of MRI abnormalities was the RV free wall (9 patients), whereas only 3 patients demonstrated abnormalities in the structure or function of the RVOT. There was a poor correlation between the site of MRI abnormalities and the origin of VT defined by pace mapping and VT morphology (Table 3). Of 10 patients with an arrhythmogenic focus that mapped to the RVOT, isolated focal abnormalities were detected by MRI in the RV free wall in 5 and in the RVOT in 1; 2 patients demonstrated abnormalities in both the RV free wall and RVOT, and 2 were normal.

Fatty infiltration was noted in the RV free wall in 3 patients and in the RVOT in 1 patient. In general, these were focal intramural lesions, and diffuse transmural replacement with adipose tissue was not observed. Two patients with focal adipose lesions in the RV free wall also had associated thinning and focal hypokinesis of the free wall. In patient 6, who presented with repetitive monomorphic VT localizing to the RVOT and a surface ECG notable for an RV conduction delay with anterior T-wave inversions, fatty infiltration with apical thinning and focal hypokinesis were noted in the RV free wall (Fig 9).

The presence of MRI abnormalities did not correlate with age, clinical presentation (sustained VT versus RMVT), duration of symptoms, number of radiofrequency applications, or interval between ablation and MRI scanning. Abnormalities were detected in two patients who were not subject to ablation, including focal fatty infiltration in the RV free wall of a 7-year-old boy (patient 9) and focal thinning and dyskinesis in the RV free wall of a 46-year-old woman (patient 3). In both patients, the morphology of VT was LBBB inferior axis, which is consistent with an RVOT origin.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
The major finding of this study is that despite similarities in electrophysiological properties, patients with idiopathic adenosine-sensitive VT comprise a heterogeneous population as assessed by MRI. Abnormalities in the RV, such as focal wall thinning, fatty infiltration, and regional wall motion abnormalities, were present in 71% of the patients studied, whereas only 1 control subject demonstrated thinning of the RV free wall (6%). These findings were present despite normal results obtained with conventional imaging. However, it is unlikely that the structural abnormalities identified by MRI are causally related to adenosine-sensitive VT because the location of these abnormalities did not correspond to the electrophysiologically defined VT origin and no abnormalities were observed in nearly 30% of patients.

Structural Abnormalities in Idiopathic VT
The definition of idiopathic VT is based on the absence of structural heart disease and depends on the diagnostic modalities used to assess cardiac structure. Previous studies have used echocardiography, RV angiography, endomyocardial biopsy, and the signal-averaged ECG to demonstrate that a substantial minority of patients with RV tachycardia have structural abnormalities in the RV.^{2 3 5 7} In these studies, the response to adenosine was not assessed, and it is likely that the populations studied were heterogeneous with respect to the tachycardia mechanism. For example, in a report of 10 patients with VT arising from the RVOT, three presumptive mechanisms were identified: reentry, automaticity, and triggered activity.¹² In contrast, studies in patients with adenosine-sensitive VT have demonstrated no structural abnormalities as defined by echocardiography, angiography, signal-averaged ECG, and myocardial biopsy.^{20 21 22 23}

More recently, MRI has been used to detect subtle wall motion and structural abnormalities in the RV in patients with tachycardia arising from the RVOT.^{16 18 19} The results of these studies are inconsistent. For instance, a total of 16 patients with RVOT tachycardia had normal static MRI scans in previous series.^{13 14 15} In contrast, Carlson et al¹⁸ demonstrated focal wall thinning, excavation, and decreased systolic thickening in 95% of patients with VT originating from the RVOT, although RV function was normal as assessed by echocardiography. In their study, the most common site of abnormality was the RVOT, but they also observed abnormalities in the RV free wall and RV apex. Their findings differ from our data in several respects. In the present study, abnormalities clustered in the RV free wall rather than the RVOT, typically at sites remote from the tachycardia origin. In addition, we identified the presence of fatty infiltration, which has not been previously described in this population. A likely explanation for this discrepancy is that a variety of mechanisms may have been responsible for RVOT tachycardia in the previous study, whereas in the present study, a homogeneous group of patients were studied with respect to VT mechanism (ie, adenosine-sensitive triggered activity).

Significance of Abnormalities
Several explanations may account for the abnormal MRI results defined in this study. One unexpected finding was focal fatty deposition in 29% of patients, suggesting the possibility that patients with adenosine-sensitive VT who manifest structural abnormalities by MRI represent a forme fruste or an unrecognized variant of ARVD. This latter entity is characterized by fibroadipose replacement of myocardial tissue in the RV,^{26 27 28} and MRI has emerged as an important diagnostic modality in these patients. Characteristic MRI abnormalities are considered to include diffuse transmural or focal fatty deposition in the RV free wall and extreme thinning of the RV wall, which may be focal or diffuse in nature.^{17 29 30 31 32} Patients with adenosine-sensitive VT and ARVD share several other features in common; these include facilitation of tachycardia by catecholamines or exercise and an RV origin, which may result in an LBBB, inferior axis VT morphology.²⁶ Of interest, 1 patient who presented with repetitive monomorphic VT demonstrated findings typical of ARVD on the surface ECG (RV conduction delay with anterior T-wave inversions). This patient was found to have fatty infiltration of the RV free wall with wall thinning and focal dyskinesis, suggesting a link between adenosine-sensitive VT and ARVD.

These two forms of VT, however, demonstrate important differences with respect to mechanism and prognosis. ARVD is thought to be due to a reentrant mechanism, which is supported by the high prevalence of late potentials detected by signal-averaged ECG^{33 34} and the consistent demonstration of entrainment.³⁵ In contrast, patients with adenosine-sensitive VT share a mechanism of tachycardia consistent with triggered activity arising from delayed afterdepolarizations and inconsistent with reentry. This is supported by termination of tachycardia with adenosine as well as sensitivity to vagal maneuvers and calcium channel blockers.^{20 21 22} We have previously shown that adenosine demonstrates mechanism-specific effects in VT, in that reentrant tachycardia such as that observed in patients with clinically and pathologically defined ARVD is insensitive to adenosine.³⁶ A focal mechanism of arrhythmogenesis in adenosine-sensitive VT is further supported by the absence of late potentials, a finding demonstrated in the present study and reported in previous series of patients with VT arising from RVOT.^{1 19 23 37} The success of radiofrequency ablation guided by pace mapping further underscores the focal nature of this tachycardia.^{12 24}

Although there is a relative paucity of data regarding the effects of pharmacological probes on VT due to ARVD, results suggest that this form of VT is insensitive to adenosine, vagal maneuvers, verapamil, and ß-blockers. We reported 2 patients with ARVD, each of whom demonstrated catecholamine-facilitated reentry, in whom adenosine had no effect on ventricular tachycardia.³⁶ Wichter et al⁴⁷ demonstrated that verapamil and ß-blockers did not prevent inducibility of VT by programmed stimulation in 5 and 8 patients, respectively, with ARVD. Thus, adenosine-sensitive VT and ARVD likely represent different electrophysiological entities. The results of this study therefore call into question the specificity of fatty deposition and wall thinning in establishing the diagnosis of ARVD.¹⁷

A second possibility is that these structural abnormalities are a secondary response to recurrent tachycardia. Tachycardia-related cardiomyopathy has been demonstrated in patients with orthodromic AV reciprocating tachycardia, atrial tachyarrhythmias, and VT.^{38 39 40 41 42} In animal models of pacing-induced cardiomyopathy, short-term pathological changes include myocyte loss, reactive hypertrophy, and replacement fibrosis in the left ventricle^{43 44} ; however, fatty replacement has not been reported. Also inconsistent with this hypothesis is that tachycardia-related cardiomyopathy typically involves both ventricles, and one would thus expect to visualize structural abnormalities in both chambers. Finally, the duration of symptoms, clinical presentation (paroxysmal VT versus RMVT), and time since successful ablation did not predict the presence of MRI abnormalities in the present study.

A final explanation is that the structural changes are secondary to an underlying pathological process that results in triggered activity and that focal fat deposition and wall thinning are nonspecific responses to injury in the RV. The basic defect in adenosine-sensitive VT, whether on a cellular or neuronal level, is not yet defined. An abnormality resulting in extensive activation of any component of the ß-adrenergic signal transduction cascade could be responsible for provoking tachycardia in these patients. One such hypothetical example would be sympathetic denervation, which would result in catecholamine hypersensitivity and potentially lead to structural abnormalities in the RV.

Study Limitations
The interpretation of fatty infiltration in the RV is confounded by the normal distribution of fat in the atrioventricular groove and epicardial surface and the introduction of factitious areas of high intensity on T1-weighted images due to artifacts from the ventricular blood pool.³² In addition, wall thinning may be difficult to interpret due to normal thinning of the RV apex and the presence of trabeculation in the RV. These technical limitations were addressed by using a saturation pulse at the level of the interventricular septum, thus minimizing T1 artifact from the underlying blood pool and enhancing the resolution of the RV free wall. Abnormal wall thickness was defined if the RV wall was <2 mm and thinner than neighboring segments, with confirmation from saturation pulse images. In addition, fatty infiltration was defined only if intense T1 signals were detected from within the myocardial wall (Fig 9). The combination of fatty infiltration, wall thinning, and wall motion abnormalities is suggestive of a pathological process. Of importance, we observed no fatty deposition in 18 clinically normal control subjects, which further supports the significance of these findings.

A potential limitation is that the MRI abnormalities observed in these patients may be a secondary effect of ablation. Histological examination of chronic radiofrequency lesions in animal models and humans has demonstrated fibrosis, granulation tissue, and fat deposition.^{45 46} However, this explanation is unlikely to account for the structural abnormalities observed in this study because the sites identified by MRI did not correspond to the sites of ablation. Ablation was guided by pace mapping, and lesions were placed in a circumscribed region, remote from the subtricuspid free wall. Finally, the number of radiofrequency applications did not predict the presence of MRI abnormalities, and structural changes, including fat, were detected in 2 patients who did not undergo ablation.

Because MRI and other imaging modalities were not performed at the same time, we cannot compare the relative yields of each modality in detecting subtle anatomic abnormalities. In several patients, however, each test was obtained within a short time (patients 12 to 14), and MRI emerged as the most sensitive modality.

Clinical Implications
The findings of this study raise questions with regard to the specificity of MRI-defined fatty deposition, wall thinning, and abnormal wall motion in the diagnosis of ARVD. The functional significance of these anatomic abnormalities remains uncertain, particularly because nearly 30% of patients had no abnormalities defined in this study. In addition, the prognostic implications of these findings have yet to be established. It is unknown whether these structural abnormalities will herald future sites of de novo arrhythmias or if they will remain physiologically unimportant. Serial MRI scans will be important in addressing this question and defining the natural history of adenosine-sensitive VT.

	Selected Abbreviations and Acronyms

 

ARVD = arrhythmogenic right ventricular dysplasia AV = atrioventricular LAS = low-amplitude signal LBBB = left bundle-branch block LV = left ventricular, left ventricle LVOT = left ventricular outflow tract MRI = magnetic resonance imaging RBBB = right bundle-branch block RMS = root-mean-square RMVT = repetitive monomorphic ventricular tachycardia RV = right ventricular, right ventricle RVOT = right ventricular outflow tract VT = ventricular tachycardia

	Acknowledgments

 
This work was supported in part by a grant from the National Institutes of Health (RO1-44747) and the Rosenfeld Heart Foundation. Dr Lerman is an Established Investigator of the American Heart Association.

Received September 30, 1996; revision received February 20, 1997; accepted March 11, 1997.

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