Value of the 12-lead electrocardiogram in arrhythmogenic right ventricular dysplasia, and absence of correlation with echocardiographic findings

Value of the 124ead Electrocardiogram in Arrhythmogenic Right Ventricular Dysplasia, and Absence of Correlation with Echocardiographic Findings JacquesT. Metzger, MD, Christian de Chillou,MD, Emile Cheriex, MD, Luz-MariaRodriguez,MD, Joep L. R. M. Smeets, MD, and Hein J. J. Wellens,MD

A

rrhythmogenic right ventricular (RV) dysplasia is characterized by a combination of replacement of RV myocardium by adipose and fibrous tissue,ra2 and ventricular arrhythmias. The disease, lirst reported in 1977 by Fontaine et al,3 was reviewed extensively by Marcus et al* in 1982. The electrocardiographic pattern of ventricular tachycardia (VT) in arrhythmogenic RV dysplasia has been reported by different investigatorsG but the value of the 1Zlead electrocardiogram to identify arrhythmogenic RV dysplasia during sinus rhythm has not been described in a large series of patients. The aims of the present retrospective study were to assess the value of the 1Zlead electrocardiogram during sinus rhythm in the diagnosis of arrhythmogenic RV dysplasia and study the possible value of serial electrocardiographic recordings to recognize progression of arrhythmogenic RV dysplasia over time.

The 12-lead electrocardiogram during sinus rhythm was studied in 20 patients with anhythmogenic right ventricular (RV) dysplasia with symptomatic ventricular tachycatdia. Findings were analyzed, together with echocardiographic evaluation of site, extent and progression of RV wall abnonnalities. Electrocardiographic abnormalities were found in 90% of patients. No correlation was found between abnormalities on the initial 12-lead electrocardiogram, and the echocardiographic extent and location of RV involvement. Over time, echocardiographic progression of the disease was observed; RV size increased in 6 of 7 patients from 34 + 3 to 39 +- 3 mm (p = O.Ol), and there was progression in the extent of RV wall motion abnormalities in 4 of 7 patients. Analysis of serial electrocardiographic recordings did not reveal changes indicative of progression of the disease during followup of 71 f 46 months. R is concluded that electrocardiographic abnormalities suggesting arrhythmogenic RV dysplasia are present in 90% of symptomatic patients on the first elee trocardiogram recorded during sinus rhythm. However, serial electrocardiographic recordings in these patients do not provide information regarding anatomic progression of the disease. (Am J Cardiol1993;72:964-967)

METHODS

From the Department of Cardiology, Academic Hospital, University of Limburg, Maastricht, the Netherlands. This study was supported by a grant from the Wynand M. Pon Foundation, Leusden, the Netherlands. Dr. Metzger is also supported by a grant from the Swiss Science Foundation, Bern, Switzerland. Manuscript received December 31, 1992; revised manuscript received and accepted June 2, 1993. Address for reprints: Jacques T. Metzger, MD, Department of Cardiology, Academic Hospital, PO Box 5800, 6802 AZ Maastricht, the Netherlands.

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Patients: Between January 1979 and March 1992, 20 patients with documented sustained monomorphic VT due to an arrhythmogenic RV dysplasia were referred to our institution for evaluation and treatment. In all patients, the diagnosis of arrhythmogenic RV dysplasia was obtained by RV wall motion abnormalities on 2-dimensional echocardiography. The history and clinical data of these patients did not reveal any associated cardiac disease. There were 19 male and 1 female patient, with a mean age of 30 ): 15 years (range 14 to 69) at the onset of symptoms. We previously reported the clinical data and outcome of 12 of these patients.7 ElectrocaMographic recouli~@ Several 12-lead electrocardiograms using a paper speed of 25 mm/s were recorded in sinus rhythm during admission to our department and during control visits to the outpatient clinic. Only electrocardiographic registrations obtained >l month after a clinically recognized or documented VT episode were examined to avoid post-VT repolarization changes. Mean age at the frrst qualifying elecn-ocardiogram was 36 f 16 years (range 16 to 72). Time interval between the onset of arrhythmic symptoms and the first electrocardiogram was 6 f 7 years (range 0.1 to 25.0); in 14 patients, follow-up electrocardiograms recorded 6 to 149 months later (mean 71 + 48) were available for comparison. In 1 patient, atria1 fibrillation was present during follow-up electrocardiographic re-

OCTOBER X,1993

TABLE

I Initial Electrocardiographic

Parameters

P Wave in II Patlent 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 ~

Age (yr) & Sex

Width (ms)

During

Sinus

Rhythm,

and Echocardiographic

QRS Complex

Voltage (mV)

Width (ms)

16M 19M

80

0.20

90

0.10

110 90

20M 23M 23M 25M 26M 26M 27M 31M 33M 40F 40M 45M 46M 47M 50M 54M 68M 72M

100 90 100 100 80 80 120 100 100 120 130 100 115 100 100 130 90 110

0.20 0.10 0.20 0.10 0.20 0.10 0.10 0.20 0.20 0.30 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.20

110 90 120 100 110 110 100 110 100 110 120 110 110 100 110 120 120 110

Axis (“) Pd 70 80 -15 20 Pd 60 40 30 110 30 150 45 70 -30 0 90 10 80 90

R Peak Time in VI (set)

I-RBBB

0.07 0.03 0.08 0.03 0.01 0.04 0.02 0.02 0.02 0.02 0.03 0.04 0.02 0.04 0.03 0.03 0.02 0.04 0.06 0.02

+ 0 + 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 + 0

Findings Precordial Leads with Negative T Waves

I = initialexaminabon; I-RBBB = mcompletenght bundle branch block; II = lastexamination; Pd = perpendiculartofrontal = missing.

cording. At the time of the electrocardiographic recordings, 17 patients were receiving medication. Class III drugs (amiodarone or sotalol) were the most frequently prescribed medications (n = 9). Class II drugs (metopro101 or acebutol) were received by 4 patients and class I drugs (class Ia: aprindine [n = 21; and class Ic: propafenone [n = 23) by 4. One patient was treated with a class IV agent (bepridil), and 1 had a combination of amiodarone and digitoxin. With the exception of those with aprindine and bepridil at the time of the initial recording, all patients were maintained on the same medication during the follow-up period. Using previously published definitions and normal values,s-9the IZlead electrocardiogram was classified as to: (1) width of the P wave in lead II (>I20 ms); (2) voltage of the P wave in lead II (>0.20 mV); (3) PR interval (>200 ms); (4) QRS width (>I10 ms); (5) presence of complete or incomplete right bundle branch block defined as a QRS duration R-wave duration or >40 ms); (6) frontal QRS axis; (7) QRS voltage in limb leads; (8) QRS voltage in precordial leads; (9) time from the onset of the QRS to the summit of the R wave (R peak time) in lead V1 (>0.04 second)‘O; and (IO) polarity of the T wave in all precordial leads. A normal frontal QRS axis was defined as located between -30” and +75”, a superior axis as ranging from -30” to -IgO”, and an inferior axis as ranging from +75” to -180”. A low voltage in the limb leads was defined by a QRS voltage IO.5 mV in any limb lead. A low voltage in the precordial leads was defined as a QRS voltage 10.7 mV in any precordial lead. T-wave polarity was considered as abnormal if negative in any precordial lead, except VI and VZ.~ We scored electrocardiographic abnormalities by giving 1 point to each pathologic finding and adding them (maximal theoretical score = IO). All elecEocardiograms were ana-

Vl Vl v1tov5

VI to v5 v1tov3 v1tov5 v1tov3 Vl to V6 VI tov4 Vl to v5 Vl tov4

0 v1tov3

VI v1tov5 Vl to VP v1tov4 v1tov3

Vl to V6 Vl

RV Size (mm) I 34 42 40 38 38 34 36 46 28 34 36 44 60 36 47 40 40 38 60 40

Echo Score

II

I

36

-

1 11

40 40 36 37 40 43 -

556 4 9 99 7 12 911 37811 513 5-

II 3 -

6 7 9 9 10 13 -

-

plane; RV = right ventricular; + = present: 0 = absent;

lyzed without knowledge of findings on the 2-dimensional echocardiogram. Twodimensional echocardiogram: An echocardiographic examination was performed in all patients. The time interval between the -6rst IZlead electrocardiogram and the echocardiographic evaluation was 23 f 41 months (range 0 to 136; <3 for 12 patients). The 2-dimensional echocardiographic examinations were performed using an HP Sonos 500 or 1000 with a 2.5 mHz transducer and stored on videotape. The basic investigation included standardized measurements in M-mode and 2-dimensional echocardiography, according to the recommendations of the American Society of Echocardiography.’ ’ RV dimension was measured in the apical 4-chamber view at the level of the tricuspid valve. Special attention was given to aspect and motion of the ventricular wall in the subcostal view of the right ventricle. All tapes were reviewed and specifically examined for: (1) location of RV wall motion abnormality (outflow, inferobasal or apical), (2) pattern of wall motion abnormality (hypokinesia, akinesia or dyskinesia), and (3) aspect of the moderator band. For practical purposes, echocardiographic findings were graded according to the following definitions: normal wall motion = 0; hypokinesia = 1; hypokinesia to akinesia = 2; akinesia = 3; akinesia to dyskinesia = 4; and dyskinesia = 5. All findings were then added to produce an echocardiographic score. Statistical analysisz Continuous variables were analyzed using a paired t test. Data are presented as mean + SD. Noncontinuous variables were analyzed with chisquare test. Statistical significance was assumed for p values 50.05. RESULTS Initial 124ead electrocardiogram

(Table I): In 90%

of patients (18 of ZO), we could find Zl abnormality

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among the 10 electrocardiographic parameters studied. In 3 patients, the only abnormality was T-wave negativity in the precordial leads. In all other patients, 22 abnormal electrocardiographic parameters were present. Figure 1 shows an example of a typical 1Zlead electrocardiogram in a patient (no. 15) with arrhythmogenic RV dysplasia. Echocardiographic examination: The results of the 2-dimensional echocardiogram are listed in Table I. Half of the patients (10 of 20) had an RV size 240 mm. In

TABLE II Comparison Between Electrocardiographic Echocardiographic Findings (n = 20)

and

Electrocardiographic

Echocardiographic score 1 to 6 7to15 Right ventricular size <40mm 240 mm

TABLE Patients:

Ill

Findings Follow-Up

r3

3 7

5 5

6 4

4 6

on Serial

Electrocardiograms

6 to 149

Months

(mean

First Electrocardiogram Atrial abnormality PR interval (ms) Abnormal PR interval QRS width Ims) Abnormal QRS width Abnormal QRS axis Abnormal R peak time in V1 Incomplete right bundle branch block Low voltage Limb leads Precordial leads Inverted T waves in VI to V3

1 165 f 31 2 107 2 10 9 4 6 3

Correlation between 124ead electrocerdiogram and echocardiographic findings: No association was

Score

<3

in 14

71 f 48) Last Electrocardiogram 1 173 2 36 1 106 f 9 7 5 5 3

2 0 11

Initial 124ead electrocardiogram during sinus rhythm: In this group of patients referred to our institu-

4 1 9

tion for evaluation of sustained monomorphic VT, the diagnosis of arrhythmogenic RV dysplasia was based on documentation of a VT originating in the right ventricle associated with echocardiographic abnormalities. Analysis of the initial 1Zlead electrocardiogram during sinus rhythm showed abnormal findings in 90% of patients. In 15 of 20 patients, >l electrocardiographic abnormality was present. The most frequent linding, as previously reported by other investigators,2 was the presence of negative T waves in the precordial leads. Three of the present patients had an inverted T wave in the precordial leads as their only abnormality. Because the qualifying electrocardiogram was recorded >l month after a clinically recognized or documented VT, it is unlikely that these T-wave abnormalities were due to post-VT repolarization changes. l3 Prolongation of QRS duration (2110 ms) was found in 14 of 20 patients. Marcus, Frank and Fontaine et a12,4J4J5previously noted an increase in QRS width, described the delay in conduction over the right ventricle (their so-called postexcitation or Epsilon waves), and demonstrated that the signal-averaged electrocardiogram during sinus rhythm showed increased duration and a terminal portion with low voltage. Be-

avl

FlGURE 1. Twelvdead electrocardiogram rhythm showing QRS duration of 110 waves from leads V, to V,. THE AMERICAN

JOURNAL

found between the echocardiographic severity or extent of disease in the right ventricle and the electrocardiographic abnormalities during sinus rhythm. Furthermore, no relation was present between the size of the right ventricle and the 1Zlead electrocardiographic abnormalities (Table II). Echocardiographic progression (Table I): In 7 patients, serial 2-dimensional echocardiograms were available for comparison. The time interval between the first and last examinations was 48 + 24 months (range 12 to 84). Worsening of abnormalities in RV wall motion was observed in 4 patients, and progression of RV size in 6 (from 34 + 3 to 39 k 3 mm; p = 0.01). Electrocdiographic ckngs Serial electrocardiographic recordings were available in 14 patients. The results are summarized in Table ILI. After a mean followup of 71 + 49 months (range 6 to 149), no statistically significant electrocardiographic changes could be shown for the 10 parameters studied. DISCUSSION

I

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90% of patients (n = 18), 2 or 3 areas with RV wall motion abnormalities were found. The inferobasal RV region was involved in all patients, whereas the outklow tract and apex were found to be abnormal in 80 and 75%, respectively. Dyskinesia was more frequently present in the inferobasal RV area (n = 14) than in other regions. A hyperechogenic (dense) moderator band was observed in 40% of patients (n = 8). Left ventricular ejection fraction was reduced in 2 patients (no. 3 = 30%; and no. 12 = 52%). Patient 3 died suddenly after exercise, and postmortem examination revealed additional fatty degeneration in the left ventricle.12 Left ventricular involvement was also found in patient 12 who died after surgery for incessant episodes of VT,

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cause our primary interest during this retrospective study was to investigate the value of the conventional 1Zlead electrocardiogram using normal standardization and filtering, we cannot comment on the signal-averaged electrocardiogram in our patients. Dilatation of the right ventricle with fatty degeneration and loss of muscle cells is the most probable mechanism for QRS prolongation. An additional role could have been played by the medication used at the time of electrocardiographic recording. An incomplete right bundle branch block was present in only 3 patients (15%), but 7 (35%) showed widening of the initial positivity in lead Vt (prolonged R peak time). This may reflect local delay in RV activity. No correlation was observed between the location of the pathologic process in the right ventricle and prolongation of the R peak time. A right-axis deviation could be observed in 30% of patients, which is in accordance with a previous report2 All these patients had an enlarged right ventricle. Low voltage in the limb leads was found in only 4 patients, I of whom had clear involvement of the left ventricle with diminished left ventricular function. Correlation between the l&lead electrocerdi~ gram and echocardiographic findings: No correlation

was found between the echocardiographic extent of disease and the number of abnormalities on the 1Zlead electrocardiogram during sinus rhythm. This finding could theoretically be due to the time interval between the electrocardiographic recording and echocardiographic examination. However, in 60% of patients, this interval delay was 13 months. Echocerdiographic progression: In 7 patients, repeated echocardiographic examinations were available for review. Over time, progression of preexisting wall motion abnormalities was observed in 3 patients, whereas a new region with wall motion abnormalities was found in 1. This suggests the presence of progression of disease in these patients. Absence of electrocardiographic changes during follow-up: In 14 of 20 patients, several electrocardio-

grams during sinus rhythm were recorded over time. During a relatively long period of follow-up, we found neither a change in the 10 electrocardiographic parameters examined nor an increase in the number of electrocardiographic abnormalities. This was also the case in 4 patients in whom echocardiographic progression of the disease could be documented. Absence of progression of electrocardiographic abnormalities may have been due to the unknown time delay between the onset of the disease in the right ventricle and the first recorded electrocardiogram. At the time of the initial electrocardiographic recording, the pathologic process in the right ventricle may already be so far advanced that subsequent anatomic changes will not result in additional electrocardiographic changes. However, we do not have signal-averaged electrocardiograms in most of our patients and therefore are unable to comment on the possibility of progressive changes in the signal-averaged elec-

trocardiogram, especially in its latter portion. However, Blomstrom-Lundqvist et all6 could not show statistically significant changes over time on repeated signal-averaged electrocardiograms. Study limitations: This retrospective study focuses on findings in symptomatic patients with RV dysplasia presenting with serious ventricular arrhythmias. The study does not examine the value of the 1Zlead electrocardiogram to diagnose RV dysplasia when the patient is asymptomatic. Furthermore, most patients were receiving antiarrhythmic medicine that may have affected QRS duration and ST-T segments. However, most patients receiving a&u-rhythmic medication were continued on the same drugs during the study. Therefore, the conclusion that follow-up electrocardiograms are of no value in documenting the presence of progression of RV dysplasia remains valid.

1. Guiraudon CM. Histological diagnosis of right ventricular dysplasia: a role for electron microscopy? Eur Heart J 1989;10:95-96. 2. Marcus FI, Fontaine GH, Guiraudon G, Frank R, Lawenceau JL, Malergue C, Grosgogeat Y. Right venhicular dysplasia: a report of 24 adult cases. Circukzrion 1982;65:384-387. 3. Fontaine GH, Guiraudon G; Frank R, Vedel .I, Grosgogeat Y, Cabrol C, Facquet J. Stimulation studies and epicardial mapping in ventricular tachycardia: study of mechanisms and selection for surgery. In: Kulberms H, ed. Reentrant Arrhyrhmiss. Lancaster, UK: MTP Publishing, 1977:334350. 4. Frank R, Fontaine GH, Vedel J, Mialet G, Sol C, Guiraudon G, Grosgogeat Y. Electroctiiographie de quatre cas de dysplasie ventriculaire droite atythmog&ne. Arch Mal Coeur 1978;9:963-972. 5. Proclemer A, Ciani R, Feruglio GA. Right ventricular tachycardia with left bundle branch block and inferior axis morphology: clinical and arrhythmological characteristics in 15 patients. face 1989:12:977-989. 6. Leclerca JF. Coumel P. Characteristics. oroznosis and treatment of the ventricular xrhyimias of right ventricular dyspla&.kur Hean J 1989;10:61+7. 7. Lemery R, Bmgada P, Janssen J, Cheriex E, Dugemier T. Wellens HJJ. Nonischemic sustained ventricular tachycardia: clinical outcome in 12 patients with arrhythmogenic right ventricular dysplasia. .I Am Coil Cardiol 1989;14:9&105. 8. Macfarlane PW, Veitch Lawrie TD. The normal electrocardiogram and vectocardiogram. In: Macfarlane PW, Veitch Lawrie TD, eds. Comprehensive Electrocardiology. Theory and Practice in Health and Disease. New York: Pergamon Press, 1989:407-457. 9. Macfarlane PW, Veitch Lawrie TD. Appendix 1. Normal limits. In: Macfarlane PW, Veitch Lawrie TD, eds. Comprehensive Elec~rocardiology Theory and Practice in Health and Disease. New York: Pergamon Press, 1989:1441-1526. 10. Willems IL, Robles de Medina EO, Bernard R, Coumel P, Fisch C, Krikler D, Mazur NA, Meijler FL, Mogensen L, Moret P, Pisa Z, Rautaharju PM, Surawicz B, Watanabe Y, Wellens HJJ. Criteria for intraventricular conduction distw bances and pre-excitation. J Am Coil Cardiol 1985;5:1261-1275. 11. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgsell H, Reichek N, S&n D, Schnittger I, Silverman NH, Tajiik J. Recommendations for quantification of the left ventricle by Z-dimensional echocardiography. American Society of Echocardiography. Committee on Standards. Subcommittee on Quantification of Z-Dimensional Echocardiograms. J Am Sot Echocardiogr 1989:2:6:358-367. 12. Cruz FES, Have&h M, Bmgada P, Atie J, Cheriex EC, Smeets JLRM, Janssen J, Wellens HJJ. Pathologic findings after sudden death in arrhythmogenic right ventricular dysplasia. Am fCardi&sc Path01 1990,3:229-232.. 13. Rosenbaum MB, Blanco HH. Eliti MV, Lzizzti, Davidenko JM. Electronic modulation of the T wave and cardiac memory. Am .I Cardiol 1982;50:213-222. 14. Fontaine G, Frank R, Gallais-Hamonno F, Allali I, Phan-Thuc H, Grosgogeat Y. Electrocardiographic des potent& tardifs du syndrome de post-exitation. Arch MaZ Coeur 1978;8:854-864. 15. Fontaine G. Frank R. Guiraudon G. Pavie A. Tereau Y. Chomette G. Grosgogeat Y. Signification de; troubles de conduction intravenuiculaires observ& dans la dysplasie ventriculaire droite arythmogkne. Arch Ma! Coeur 1984;8:872-879. 16. Blomstrb;m-Lundqvist C, Olsson SB, Edvardsson N. Follow-up by repeated signal-averaged surface QRS in patients with the syndrome of arrhythmogenic right venhicular dysplasia. Eur Hearf .I 1989;10:5460.

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