2001;38;364-370 J. Am. Coll. Cardiol.C. Rosa Brusin, Giuseppe Molinari, and Giampaolo Trevi

Fiorenzo Gaita, Carla Giustetto, Paolo Di Donna, Elena Richiardi, Luigi Libero, Maria Long-term follow-up of right ventricular monomorphic extrasystoles

This information is current as of July 12, 2011

http://content.onlinejacc.org/cgi/content/full/38/2/364located on the World Wide Web at:

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Long-Term Follow-Up of RightVentricular Monomorphic ExtrasystolesFiorenzo Gaita, MD,* Carla Giustetto, MD,† Paolo Di Donna, MD,* Elena Richiardi, MD,*Luigi Libero, MD,† Maria C. Rosa Brusin, MD,† Giuseppe Molinari, MD,* Giampaolo Trevi, MD†Asti and Torino, Italy

OBJECTIVES The purpose of this study was to verify in a long-term follow-up whether frequentmonomorphic right ventricle extrasystoles may progress to arrhythmogenic right ventriculardysplasia (ARVD).

BACKGROUND Frequent monomorphic right ventricle extrasystoles are generally considered benign. How-ever, in patients with this pattern, cardiac magnetic resonance (MR) has recently shownanatomical and functional abnormalities of the right ventricle.

METHODS Sixty-one patients who had been classified by noninvasive examinations as having frequentidiopathic right ventricle ectopy were contacted after 15 6 2 years (12 to 20) and submittedto clinical examination, electrocardiogram (ECG), Holter monitoring, stress test, signalaveraged ECG, echocardiography and, in 11 patients, cardiac MR. The primary end pointwas to ascertain the presence of cases of sudden death or progression to ARVD.

RESULTS At the end of the follow-up, 55 patients were alive; six died, none of sudden death; eightstated to be well but refused further examinations. The 47 patients examined had normalECG; in 24 patients (51%), extrasystoles were no longer present at Holter monitoring; latepotentials were present in up to 15% of the patients; the right ventricle was normal atechocardiography. In 8 of 11 patients (73%), cardiac MR showed focal fatty replacement andother abnormalities of the right ventricle.

CONCLUSIONS In this long-term follow-up study, no patient died of sudden death nor developed ARVD;two-thirds of the patients were asymptomatic, and, in half of the patients, ectopy haddisappeared. Focal fatty replacement in the right ventricle was present in most. (J Am CollCardiol 2001;38:364–70) © 2001 by the American College of Cardiology

Ventricular extrasystoles are a common finding in patientswith and without heart disease. In the presence of heartdisease, frequent and repetitive extrasystoles are an indepen-dent predictive factor of total mortality and sudden death(1–3). On the other hand, very frequent monomorphicventricular complexes and even bursts of ventricular tachy-cardia in subjects without evidence of heart disease aregenerally considered benign. In 1922, Gallavardin (4) firstdescribed this kind of arrhythmia. In 1969, Rosenbaum (5)defined ventricular ectopy with left bundle branch block(LBBB) morphology and the main QRS forces directedinferiorly as “typical for normal subjects.” This kind ofextrasystole is more frequent during the day than it is atnight and is transiently suppressed by sinus tachycardia (6).The site of origin is most often the right ventricular outflowtract and, to a lesser extent, the interventricular septum (7).In the majority of these patients, echocardiography does notidentify structural cardiac abnormalities (8). More recently,however, using cardiac magnetic resonance (MR) imaging,a high prevalence of fatty replacement and other anatomicand functional abnormalities has been demonstrated inpatients with apparently idiopathic right outflow tracttachyarrhythmias (9–11). A partial overlap exists betweenthe area involved in arrhythmogenic right ventricular dys-plasia (ARVD) and idiopathic right ventricular ectopy. The

infundibulum is one of the sites most frequently involved inARVD, together with the diaphragmatic and apical walls(12). As the latter is a progressive disease (13–16), thequestion arises whether idiopathic right ventricular ectopycould be an early manifestation of ARVD. Arrhythmogenicdysplasia is easy to recognize when the right ventricle isextensively involved, but initial forms could be missed.Some patients with apparent idiopathic right ventriculararrhythmias, therefore, might be affected at an early stage.

In this study, patients with a diagnosis of idiopathic rightventricular ectopy, established through clinical examinationand noninvasive tests, were evaluated after a follow-up of atleast 12 years to verify the occurrence of sudden death andthe possible evolution towards ARVD.

METHODS

From all patients with ventricular ectopy who were evalu-ated at the University of Torino between January 1980 andOctober 1987, we selected those having extrasystoles withLBBB morphology or positive QRS from V1 to V6 at 12-leadelectrocardiogram (ECG), suggesting a right ventricular orseptal origin, in whom no clinical evidence of heart diseasewas found after routine cardiac examination, including12-lead ECG, chest X-ray and echocardiography. Patientswere referred to our center because of palpitations or thedetection of ventricular extrasystoles on a routine ECG.No patient had syncope nor near-syncope. These patientshad .40/h (.1,000/24 h) monomorphic ventricular extra-

From the *Department of Cardiology of the Civil Hospital of Asti, Asti, Italy; andthe †University of Torino, Torino, Italy.

Manuscript received November 21, 2000; revised manuscript received April 13,2001, accepted April 26, 2001.

Journal of the American College of Cardiology Vol. 38, No. 2, 2001© 2001 by the American College of Cardiology ISSN 0735-1097/01/$20.00Published by Elsevier Science Inc. PII S0735-1097(01)01403-6

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systoles, occurring at sinus rates between a critical upper andlower range, determined by observing the relation betweenthe number of extrasystoles and heart rate variations onHolter monitoring. There were occasional ventricular cou-plets and triplets in some patients; no more complexventricular arrhythmias were documented. Ectopy disap-peared during stress test. Based on these criteria, a diagnosisof idiopathic right ventricular ectopy was made. All theevaluations had been performed in the absence of anti-arrhythmic therapy, including beta-blockers.

These patients were contacted again between May 1999and February 2000. We obtained a complete medicalhistory, clinical examination, ECG, 24-h Holter monitor-ing and treadmill exercise test (Bruce protocol). Extra-systoles were considered no longer present if they were,100/24 h. Echocardiography was performed using anUltramark 9 (Advanced Technology Laboratory, Bothell,Washington) and a Sonos 2000 (Agilent Technologies, PaloAlto, California). Short- and long-axis views were obtainedin the left parasternal, apical and subcostal locations. Thediameter of the outflow tract of the right ventricle wasevaluated in the parasternal short-axis view. Longitudinaland transverse diameter and the area of the right ventriclewere taken in the long-axis four-chamber view. Signalaveraged ECG (SAECG) was performed using the 1200EPX Model (Arrhythmia Research Technology Inc., Aus-tin, Texas). Two hundred to 300 beats were averaged toobtain a noise level ,0.2 mV. Two high-pass filter settingswere used at 25 Hz and 40 Hz (17). Late potentials wereconsidered to be present if two of the three criteria weremet. A random subgroup of 11 patients was also investi-gated with cardiac MR. The study was performed using a1.5 T superconducting magnet with 25 mT/m gradients(Magnetom Vision, Siemens, Erlangen, Germany). Themorphologic study was performed in the short- and long-axis planes through breath hold single slice turbo-spin echosequences (time of echo 32 ms), with and without spectralfat-suppression. The functional study was performedthrough velocity flow refocused gradient-echo sequences(cine MR): two long-, two short-axis and one sagittal planeswere chosen; a time of echo 4.8 ms and a flip angle of 20°were used (18).Statistical analysis. Data were expressed as mean 6 SD.Student t test for paired data was used to compare thenumber of extrasystoles at enrollment and at follow-up 24-h

Holter monitoring. Student t test for unpaired data wasused to compare age at enrollment between the patients whosurvived and the group who died. A two-tailed p value of#0.05 was considered significant. Survival analysis wasperformed with the Kaplan-Meier method.

RESULTS

Sixty-one patients (30 women and 31 men) were included inthis study. At enrollment, mean age was 44 6 15 years; 55complained of palpitations, and 6 were asymptomatic.Twelve-lead ECG was normal, including QT interval, in allpatients. The morphology of the extrasystoles was LBBBand vertical axis in 52 patients (85%), LBBB and left-axisdeviation in 1 and positive QRS from V1 to V6 (right bundlebranch block [RBBB]) and left-axis deviation in 8 (Fig. 1).The mean number of extrasystoles/h at 24-h Holter mon-itoring was 526 6 456 (range 66 to 2,260). Fifty patients(82%) had ectopy at stress test basal ECG, which disap-peared in all with variable degrees of heart rate increase;extrasystoles appeared during recovery in 2 of the 11patients who did not show ectopy before exercise. Echocar-diogram was normal in all but two patients: one patient hadmitral valve prolapse without regurgitation, and the otherhad rheumatic mitral stenosis without hemodynamic rele-vance. Because of the apparent absence of relationship withectopy originating from the right outflow tract, these lattertwo patients were included in the study.

At a follow-up ranging from 12 to 20 years, mean 15years 6 2 years, 55 patients (90%) were alive, and 6 patientsdied (10%). Mean age at the first visit was 40 years 6 14years in the patients who survived and 65 years 6 10 yearsin the group who died (p , 0.001). Survival analysis showeda mortality rate of 3% at 5 years, 7% at 10 years and 10% at15 years. No patient died more than 13 years after the firstevaluation. Of the six patients who died, none died sud-denly; one died from lung cancer, one from myocardialinfarction (MI), one from stroke, two from multiorganfailure and one in a car accident. Eight patients stated thatthey were asymptomatic and in good health but declined theinvitation to undergo further examinations. None of themwas taking antiarrhythmic therapy. Forty-seven patientsagreed to be evaluated. The results of the examinations ofthis group of patients at enrollment into the study and atfollow-up are reported in Table 1. Six patients had devel-oped hypertension, and two had developed ischemic heartdisease (inferior MI and unstable angina, both treated withrevascularization); one patient developed a moderate aorticincompetence. The functional class was unchanged in thepatient with the mild mitral stenosis. Only 15 of the 47patients (32%) still had palpitations. None had been admit-ted to a hospital or had been otherwise found to havesustained ventricular tachycardia. No patient was takingantiarrhythmic drugs. Twelve-lead ECG was normal in all,except in the one who had an MI during the follow-up. Thispatient had Q-waves in the inferior leads. At 24-h Holter

Abbreviations and AcronymsARVD 5 arrhythmogenic right ventricular dysplasiaECG 5 electrocardiogramLBBB 5 left bundle branch blockMI 5 myocardial infarctionMR 5 magnetic resonanceRBBB 5 right bundle branch blockSAECG 5 signal averaged electrocardiogram

365JACC Vol. 38, No. 2, 2001 Gaita et al.August 2001:364–70 Right Ventricle Extrasystoles

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Figure 1. Twelve-lead electrocardiograms showing ventricular premature beats with left bundle branch morphology and vertical axis (top) and with positiveQRS from V1 to V6 (bottom).

366 Gaita et al. JACC Vol. 38, No. 2, 2001Right Ventricle Extrasystoles August 2001:364–70

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Yes

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112

2,67

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No

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542

AN

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127

3,04

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Yes

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661,

573

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20N

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Yes

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Yes

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No

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367JACC Vol. 38, No. 2, 2001 Gaita et al.August 2001:364–70 Right Ventricle Extrasystoles

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monitoring in 24 of the 47 patients (51%), extrasystoleswere no longer present (,100/24 h), while 9 patients (15%)still had more than 40 extrasystoles/h; the mean number ofextrasystoles/h was 68 6 176 (p , 0.001 vs. enrollment),range 0 to 868.

Stress test was performed in 47 patients: ectopy wasabsent at resting ECG in 32 (68%); in two of the patients,ectopy appeared at recovery time, and, in three patients,extrasystoles with different morphology were observed dur-ing the test. Of the 15 patients (32%) who presented ectopyon the ECG at rest, 10 showed the disappearance of theextrasystoles with variable degrees of heart rate increase. Infour patients, the ectopy persisted during the test: themaximal heart rate in these patients was lower than it was inthe stress test at enrollment. In one patient who hadaccelerated idioventricular rhythm with RBBB and left-axismorphology alternating with sinus rhythm at basal ECG,acceleration of the ventricular rate in the range of ventriculartachycardia occurred. After stopping the exercise, the tachy-cardia slowed down again to idiopathic ventricular rhythmalternating with sinus rhythm.

Signal averaged ECG was obtained in all patients; criteriafor late potentials were present in four patients (9%) when ahigh-pass filter of 25 Hz was used and in seven patients(15%) when the high-pass filter was set at 40 Hz. Echocar-diography showed moderate aortic incompetence in a hy-pertensive patient, inferior akinesia in the patient with MIand a further mitral valve prolapse without incompetence; itwas unchanged in the other cases. No abnormalities of theright ventricle were observed.

At cardiac MR (Table 2), only three patients had acompletely normal pattern. Focal adipose replacement wasfound in 8 of 11 patients (three areas in one patient, twoareas in five and one area in two) (Fig. 2); right ventricledyskinesia occurred in two patients; thin right ventricle freewall and trabecular disarray were found in one case each.One patient showed all the described abnormalities: focal

fatty tissue replacement of the outflow and posterobasaltract, right ventricle dilation and dyskinetic and thin freewall. This patient had a normal echocardiogram, absence oflate potentials and disappearance of extrasystoles atfollow-up 24-h Holter monitoring.

DISCUSSION

Ventricular extrasystoles are commonly observed in theambulatory population. Their prognostic significance de-pends largely on the presence of heart disease (1–3).Ventricular ectopy originating from the right ventricle insubjects without underlying heart disease has been knownfor a long time and is generally considered benign. How-ever, cardiac MR imaging has recently shown a highincidence of focal right ventricular abnormalities in thispopulation (9–11). The clinical meaning of these findings isstill unclear. Ventricular arrhythmias of right ventricleorigin could be the expression of an early form of ARVD.This condition is recognized as a cause of sudden, unex-pected death, particularly in younger individuals, and thisevent may be the first presentation of the disease. In apostmortem study from northern Italy, 20% of 60 patientsunder the age of 35 years who died suddenly and unexpect-edly had histological findings consistent with ARVD (19).Large studies and long follow-up periods are needed toclarify this issue. In 1985, Kennedy et al. (20) published thefollow-up study (mean 6.5 years) of 73 apparently healthysubjects with frequent and complex ventricular ectopy. Theconclusion was that the long-term prognosis of thesepatients is similar to that of the healthy population. In ourstudy we report the follow-up lasting from 12 to 20 years for61 patients with monomorphic right ventricle extrasystoles.No patient developed ARVD; none died suddenly nor hadsustained ventricular tachycardia. At the end of thefollow-up in two-thirds of the patients, palpitations haddisappeared, and none presented ECG alterations suspi-cious of ARVD (12,21). At 24-h Holter monitoring, the

Table 2. Cardiac Magnetic Resonance

Number PtVPCs

MorphologyHolter at

Follow-Up Wall MotionRV

Diameters Fatty Replacement

1 B.M. LBBB, Va P Normal Normal Focal, outflow tract and apex2 B.M. LBBB, Va P Normal Normal No3 C.A. LBBB, Va D Normal Normal Focal, free wall4 C.A. LBBB, Va D Normal Normal No5 C.F. LBBB, Va D Dyskinetic apex Normal Focal, apex and free wall6 D.A. LBBB, La P Normal Normal No7 M.D. LBBB, Va P Normal Normal Focal, outflow tract8 N.I. LBBB, Va P Normal Normal Focal, outflow tract and apex9 P.F. RBBB, La D Normal Normal Focal, outflow tract, posterobasal and apex

10 P.I. RBBB, La P Normal Normal Focal, right and left ventricle apex11 U.M. LBBB, Va D Dyskinetic and thin

free wall, trabeculardisarray

Normal Focal, outflow tract and posterobasal

D 5 VPCs disappearance; La 5 left axis; LBBB 5 left bundle branch block; P 5 VPCs persistence; RBBB 5 right bundle branch block; RV 5 right ventricle; Va 5 verticalaxis; VPCs 5 ventricular premature complexes.

368 Gaita et al. JACC Vol. 38, No. 2, 2001Right Ventricle Extrasystoles August 2001:364–70

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disappearance of ventricular extrasystoles was observed inhalf of the population, and stress test confirmed this finding.During echocardiography no abnormalities of the rightventricle were observed. An SAECG showed late potentialsin a low percentage of patients. On the contrary, a high

sensitivity and specificity of late potentials has been reportedin patients with ARVD. The low incidence of ventricularlate potentials in our population compared with patientswith ARVD may be explained by differences in the arrhyth-mogenic substrate.

Figure 2. (A,B) Magnetic resonance turbo-spin-echo images obtained at 1.5 T in a patient with monomorphic right ventricular extrasystoles. Long-axisview demonstrating high-signal intensity at the apex of the right ventricle (arrow), without (A) and with (B) spectral fat saturation. Image A acquiredwithout spectral fat saturation, shows high-signal intensity within the right ventricle apical wall due to the presence of fatty tissue. When the same imageis acquired with spectral fat saturation (B), the high-signal intensity of fatty tissue disappears, and the fatty replacement is imaged as an area of signal voidwithin the right ventricle.

369JACC Vol. 38, No. 2, 2001 Gaita et al.August 2001:364–70 Right Ventricle Extrasystoles

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Cardiac MR imaging. At MR imaging, 8 of the 11patients showed localized adipose replacements, in contrastwith the diffuse pattern that is observed in patients withARVD (10,16). Cardiac MR has allowed the identificationof focal structural changes, which could not have beenrecognized with echocardiography and have not been ob-served in normal subjects (10); these abnormalities might bethe anatomical substrate of right ventricle extrasystoles. Asarrhythmias in these patients had not worsened during amean follow-up of 15 years, there is a low probability thatthese focal abnormalities may represent an early manifesta-tion of ARVD, which is a progressive disease (13–16).

Some patients developed a heart disease during thefollow-up. However, at enrollment there was no evidence ofmost of these diseases (hypertension, ischemic heart disease,aortic incompetence), which are probably related to aging.Nonetheless, in the presence of an abnormal substrate, theprognostic value of the ectopy may be different.

When faced with right ventricular premature contractionsin an otherwise normal ECG, we have to decide whether itrepresents a benign pattern or a possible early form ofARVD. In our study after a mean follow-up of 15 years,most of the patients are asymptomatic, showing corre-sponding reduction and, often, disappearance of the extra-systoles. Moreover, no morphologic change suggestive ofprogression to ARVD was observed. Based on the data ofour study, a normal 12-lead ECG, the monomorphicpattern of ectopy and the heart rate dependence at 24-hHolter monitoring, the suppression with increasing heartrate at stress test and the normal echocardiographic patternare sufficient to pose the diagnosis of benign right ventriclearrhythmias.Study limitations. Even if this group of patients is veryhomogeneous, 61 patients may still not be enough toexclude exceptions to this benign natural history. Moreover,some patients in our population were very young. Even if amean follow-up of 15 years is a long period of time, it maystill be short as compared with the life expectancy of theyoungest patients.

The finding of late potentials has been reported in studieson right ventricular outflow tract tachycardia (22). At thepresent time, the possibility that late potentials may predictthe progression to ARVD is not established, and theirmeaning remains to be defined.

Cardiac MR was performed only in a small percentage ofpatients because it is not recognized as a routine examina-tion for patients with ventricular extrasystoles without heartdisease. The findings are noteworthy for the high prevalenceof detected right ventricle abnormalities. However, theclinical significance needs to be confirmed in larger studies.

Reprint requests and correspondence: Dr. Fiorenzo Gaita, Di-visione di Cardiologia, Ospedale Civile, Via Botallo, 4-14100 Asti,Italy. E-mail: gaitaf@tin.it.

REFERENCES

1. Bigger JT, Fleiss JL, Kleiger R, et al. The relationships amongventricular arrhythmias, left ventricular dysfunction and mortality inthe two years after myocardial infarction. Circulation 1984;69:250–8.

2. Mukharji J, Rude RE, Poole K, et al. Risk factors for sudden deathafter acute myocardial infarction: two-year follow-up. Am J Cardiol1984;54:31–6.

3. Teerlink JR, Jalaluddin M, Anderson S. Ambulatory ventriculararrhythmias in patients with heart failure do not specifically predict anincreased risk of sudden death. Circulation 2000;101:40–6.

4. Gallavardin L. Extrasistolie ventriculaire a paroxysmes tachycardiquesprolonges. Arch Mal Coeur 1922;15:298–306.

5. Rosenbaum MB. Classification of ventricular extrasystoles accordingto form. J Electrocardiol 1969;2:289–98.

6. Leclercq JF, Rosengarten MD, Attuel P, et al. L’extrasistolie ventricu-laire idiopatique: une parasystolie ventriculaire droite protegee durythme sinusal? Arch Mal Coeur 1981;74:1249–61.

7. Coumel P, Leclercq JF, Slama R. Repetitive monomorphic idiopathicventricular tachycardia. In: Zipes DP, Jalife J, editors. Cardiac Elec-trophysiology and Arrhythmias. Orlando, FL: Grune & Stratton,1985:457–68.

8. Proclemer A, Basadonna PT, Slavich GA, et al. Cardiac magneticresonance imaging findings in patients with right ventricular outflowtract premature contractions. Eur Heart J 1997;18:2002–10.

9. Carlson MD, White RD, Trohman RG. Right ventricular outflowtract tachycardia: detection of previously unrecognized anatomic ab-normalities using cine-magnetic resonance imaging. J Am Coll Car-diol 1994;24:720–7.

10. Molinari G, Sardanelli F, Gaita F. Right ventricular dysplasia as ageneralized cardiomyopathy: findings on magnetic resonance imaging.Eur Heart J 1995;16:1619–24.

11. Globits S, Kreiner G, Frank H, et al. Significance of morphologicalabnormalities detected by MRI in patients undergoing successfulablation of right ventricular outflow tract tachycardia. Circulation1997;96:2633–40.

12. Marcus FI, Fontaine G, Guiraudon G, et al. Right ventriculardysplasia: a report of 24 cases. Circulation 1982;65:384–99.

13. Blomstrom-Lundqvist C, Sabel KG, Olsson SB. A long-termfollow-up of 15 patients with arrhythmogenic right ventricular dys-plasia. Br Heart J 1987;58:477–88.

14. Marcus FJ, Fontaine GH, Frank R, Gallagher JJ, Reiter MJ. Long-term follow-up in patients with arrhythmogenic right ventriculardysplasia. Eur Heart J 1989;10 Suppl D:68–73.

15. Jaoude SA, Leclercq JF, Coumel P. Progressive ECG changes inarrhythmogenic right ventricular disease. Evidence for an evolvingdisease. Eur Heart J 1996;17:1717–22.

16. Corrado D, Basso C, Thiene G, et al. Spectrum of clinicopathologicmanifestations of arrhythmogenic right ventricular cardiomyopathy/dysplasia: a multicenter study. J Am Coll Cardiol 1997;30:1512–20.

17. Gomes JA, Winters SL, Stewart D, Targonski A, Barreca P. Optimalbandbass filters for time domain analysis of the signal-averagedelectrocardiogram. Am J Cardiol 1987;60:1290–8.

18. Molinari G, Sardanelli F, Zandrino F, et al. Adipose replacement andwall motion abnormalities in right ventricle arrhythmias: evaluation byMR imaging. Retrospective evaluation on 124 patients. Int J CardImaging 2000;16:105–15.

19. Thiene G, Nava A, Corrado D, et al. Right ventricular cardiomyop-athy and sudden death in young people. N Engl J Med 1988;318:129–33.

20. Kennedy HL, Whitlock AJ, Sprague KM, et al. Long-term follow-upof asymptomatic healthy subjects with frequent and complex ventric-ular ectopy. N Engl J Med 1985;312:193–7.

21. Fontaine G, Umemura J, Di Donna P, et al. La duree des complexesQRS dans la dysplasie ventriculaire droite arythmogene. Un nouveaumarqueur diagnostic non invasif. Ann Cardiol Angeiol (Paris) 1993;42:399–405.

22. Grimm W, List-Hellwig E, Hoffmann J, et al. Magnetic resonanceimaging and signal-averaged electrocardiography in patients withrepetitive monomorphic ventricular tachycardia and otherwise normalelectrocardiogram. Pacing Clin Electrophysiol 1997;20:1826–33.

370 Gaita et al. JACC Vol. 38, No. 2, 2001Right Ventricle Extrasystoles August 2001:364–70

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2001;38;364-370 J. Am. Coll. Cardiol.C. Rosa Brusin, Giuseppe Molinari, and Giampaolo Trevi

Fiorenzo Gaita, Carla Giustetto, Paolo Di Donna, Elena Richiardi, Luigi Libero, Maria Long-term follow-up of right ventricular monomorphic extrasystoles

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