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The Syndrome of right bundle

branch block,

ST segment elevation

and sudden death.


 

By Andrea Nava, Bortolo Martini

 

If you wish to make comments, to receive further data or to send more details please contact:

bmartini@tiscalinet.it


 

Padua, March 10, 1999

 

The first patient with this syndrome was admitted to hospital because of ventricular fibrillation on 24 december 1980 (pt. 4 reported in Am Heart J 1989;118:1203-9)

The second one in 1984 (pt. 3), and the third one in 1995 (pt.1).

The first published image of a pt. (pt 1 of Am Heart J), with VF (and the syndrome) appeared in 1986 in the "New trends in arrhythmias" by Nava A , Scognamiglio R, Buja GF, Daliento L, Bottero M. Canciani B, Corrado D, Stritoni P, Fasoli G, Martini B, Thiene g: Arrhythmogenic right ventricle. Clinical spectrum and familiarity. 1986;2:13-19 (see fig. 5 and 6), but no details were given on the resting ECG.

We also published some incomplete data on the "Giornale Italiano di Cardiologia" in 1986 (pt 11-29 and 30): Nava A, Canciani B, Scognamiglio R, Buja GF, Daliento L, Miraglia G, Martini B, Thiene G. La tachicardia e la fibrillazione ventricolare nel ventricolo destro aritmogeno. G Ital cardiol 1986;16:741-9

In 1988 we published the first detailed written description of syndrome in two abstract in Giornale Italiano di Cardiologia:

1) Nava A, Canciani B, Martini B Buja GF. La ripolarizzazione precoce nelle precordiali destre. Correlazioni ECG-VCG-elettrofisiologia G Ital Cardiol abstract 1988 suppl 1 ;18:118

2) Martini B, Nava A, Buja GF, Canciani B, Thiene G. Fibrillazione ventricolare in apparente assenza di cardiopatia. Descrizione di 6 casi. G Ital Cardiol abstract 1988 suppl 1 ;18:136

In 1988 the first (for what we know) ecg trace of the syndrome was presented in "Mises a Jour Cardiologiques" 1988;XVII,5:157-9

In 1988, the first complete description of the syndrome, was published in the American Heart Journal (19889;118:1203-9

 

 

 

 

 

This is the first published ECG trace in Medical literature (MISES A JOUR CARDIOLOGIQUES -17 ANNEE

1988 -XVII, 5, P 157-9), of a pt. resuscitated from sudden cardiac death, and admitted to Hospital in 1984 at the age of 34 years. The pt is still alive under amiodarone therapy. He did have any relapse. (pt. 3 of Am Heart J 1989)

 

 

This is the figure published in Am Heart J 1989;118:120-1209 which proposes 6 pts affected by "idiopathic ventricular fibrillation". All the different pattern of the syndrome are documented. Pt 1 had a RBBB + St segment elevation. Pt 3 (the same published in 1987 in the figure at the top) had the so colled J wave. Pt 4 had RBB + ST elevation + LAD + first degree A-V block. In this pt., admitted to hospital because of ventricular fibrillation in 1975 and died suddenly in 1981, necropsy study demonstrated right ventricular cardiomyopathy and extensive sclerosis of the conduction system (see article in J Am Coll Cardiol 1996;27:443-8). Pt 2 and 5 had isolated ST segment elevation.

 

The syndrome described by our group is characterized by:

a- juvenile aborted sudden death

b- familial involvement

c- male predominance

-ECG patterns of:

1) different degrees of right bundle branch block

2) St segment elevation in V1-V3 (which can be an isolated pattern)

3) sometime left axis deviation

4) prolonged HV interval in the cases with major conduction abnormalities

5) frequent positive late potentials study

d- unrare demonstrable evidence after detailed examination (including necropsy in rare cases) of some concealed organic heart disesease, particularly of the right ventricle.

e- the disease rarely maps (latest data will be presented at NASPE), in the same loci of right ventricular cardiomyopathy.

 

After Aihiara in 1990, in 1992, the Brugada Brothers published 8 more patients with the same clinical and ECG syndrome, in whom (apart from HV prolongation in 4 pts), they did not evidence any significant heart disease. In 1998 the same group gave evidence of a genetic ion channel disease in some of their pts. (www.brugada.crtia.be/.)

In the following pages we present the abstract of the 3 main articles on the syndrome, and the detailed review article published in 1997 in the book: arrhythmogenic right ventricular cardiomyopathy/dysplasia. A.Nava, L. Rossi G. Thiene editors. Elsevier science BV

A complete bibliography on the syndrome is also presented at the end

 

 

 

 

 

 

 

 

 

 

 

 

LA REPOLARISATION PRECOCE DANS LE PRECORDIALES

DROITES: TROUBLE DE LA CONDUCTION INTRAVENTRICULAIRE

DROITE?

CORRELATIONS DE L'ELECTROCARDIOGRAPHIE-VECTORCARDIO-

GRAPHIE AVEC L'ELECTROPHYSIOLOGIE

A.Nava, B. Canciani, M.L. Schiavinato, B. Martini, G.F. Buja

Dep. de Cardio. Univ. De Padoue (Italie)

MISES A JOUR CARDIOLOGIQUES -17 ANNEE 1988 -XVII, 5, P 157-9

_____________________________________________________________________________________________________________________

MATERIEL E METHODES

Il s'agit de 6 sujets (4 hommes et 2 femmes) àgés de 26 a 30 ans.

L'ECG montrait un sus déclage de ST (1-4 mm) supérieur a 2 mm de V1 a V5 ou de V1 a V4.....

Chez 5 de ces sujets le diagniose de dysplasie du ventricule dorit a pu etre posé. Le sixième n'avait pas de cardiopathie mais il avait présenté un épisode de fibrillation ventriculaire. Une exploration électrophysiologique s'est imposée dans 3 cas: 2 fois à cause d'un episode de FV; le troiseè sujet etait un jeune asymptomatique dont le frère était décédé subitement......

A l'ètude electrphysiologique, on remarque au niveau du septum moyen-haut, un QRS allongé qui va de 120 à 150 msec et la dernière portion (40-50 msec) coincidait avec la partie initiale et moyenne de la ripolarisation.....

Le susdécalage de ST etait secondaire non pas à une repolarisation précoce mais du moins en partie à une dépolarisation retardée.

____________________________________________________

 

Ventricular fibrillation without apparent heart

disease: Description of six cases

 

Since 1977, six patients (five males and one female), aged 14 to 35 years, resuscitated from

Ventricular fibrillation, were referred to our department for detailed evaluation, after exclusion of

major cardiac pathologic conditions. Four patients had a family history of heart disease. Basic

ECGs showed sinus rhythm in all of them. PR interval was prolonged in one. Two patients had

complete and one had incomplete right bundle branch block. One patient had inverted t waves in V1-V3 and late potentials. Three had an upslooping ST_T segment elevation in V1-V2. The

cardiothoracic index was less than 0.5 in five and 0.50 in one. In one of the five patients studied,

the clinical episodes of ventricular fibrillation was reproduced by stimulation of the right

ventricular outflow tract during electrophysiologic study. Results of cross-sectional

echocardiography and angiography showed predominantly structural and wal motion

abnormalities of the right ventricle in five patients and slight wall motion abnormalities of the left

ventricle in two. Two pwo patients had also mitral and tricuspid valve prolapse. Coronary arteries

were normal in all five patients examined. Results of endomyocardial biopsy showed no

abnormalities in one patient, fibrosis in two, and fibrolipomatosis in one. Two patients died

during follow-up: autopsy was performed in one and results showed right ventricular

cardiomyopathy. Thus in five of these selected patients with apparently idiopathic ventricular

fibrillation, some abnormalities, predominantly of the right ventricle, were documented only after

detailed investigation; however, clinical history and some nonspecific ECG abnormalities were factors in the diagnostic procedure. (Am Heart J 1989;118;6:1203.)

 

Bortolo Martini, MD, Andrea Nava, MD, Gaetano Thiene, MD,

Gian Franco Buja, MD, Bruno Canciani, MD, Roldano Scognamiglio, MD,

Luciano Daliento, MD, Sergio Dalla Volta, MD. Padua, Italy

 

 

________________________________________________________________________________________________________

 

 

Familial Cardiomyopathy Underlies Syndrome of Right Bundle Branch Block, ST Segment Elevation and Sudden Death

 

DOMENICO CORRADO, MD, ANDREA NAVA, MD, GIANFRANCO BUJA,MD,

BORTOLO MARTINI, MD, GIUSEPPE FASOLI, MD, LUCA OSELLADORE, MD,

PIETRO TURRINI, MD, GAETANO THIENE, FESC

Padua, Italy

______________________________________________________________________________

Objectives. We sought to assess wether structural heart disease underlies the syndrome of right bundle branch block, per- sistent ST segment elevation and sudden death.

Background. Ventricular fibrillation and sudden death may occur in patients with a distinctive electrocardiographic (ECG) pattern of right bundle branch block and persistent ST segment elevation in the right precordial leads.

Methods. Sixteen membres of a family affected by this syndrome underwent noninvasive cardiac evaluation, including electrocardiography, Holter ambulatory ECG monitoring, stress testing, echocardiography and signal-averaged electrocardiography; two patients had electrophysiologic and angiographic study. Endomyocardial biopsy was performed in one living patient, and postmortem examination, including study of the specialized conduction system, was performed in one victim of sudden death.

Results. Five years before a fatal cardia arrest, the proband had been resuscitated from sudden cardiac arrest due to recorded ventricular fibrillation. Serial ECGs showed a a prolonged PR interval, right bundle branch block, left axis deviation and persistent ST segment elevation in the right precordial leads, in the absence of clinical heart disease. Postmortem investigation disclosed right ventricular dilation and myocardial atrophy with adipose replacement of the right ventricular free wall as well as sclerotic interruption of the right bundle branch. A variable degree of right bundle branch block and upslooping right precordial ST segment was observed in seven family members; four of the seven had structural right ventriccular right ventricular abnormalities on echocardiography and late potentials on the signal-averaged electrocardiography. A sib of the proband also had a prolonged HV interval, inducible ventriculat tachycardia and fibrofatty replacement on endomyocardia byopsy.

Conclusions. An autosominal dominant familial cardiomyopathy, mainly involving the right ventricle and the conduction system, accounted for the ECG changes and the electrical instability of the syndrome.

(I Am Coll Cardiol 1996;27:443-8)

_____________________________________________________________________________________________________________________

Syndrome of right bundle branch block, ST segment elevation

and sudden death: evidence of an organic substrate

 

Bortolo Martini M.D, Domenico Corrado, Andrea Nava and Gaetano Thiene

 

1997 Elsevier Science B.V.

 

In: Arrhytmogenic right ventricular cardiomyopathy/dysplasia

A.Nava, L.Rossi, G.Thiene Editors

 

Abstract:

Non-ischemic upslooping ST segment elevation in the precordial leads has been recognised for decades in electrocardiography. Early reports ascribed this pattern to a normal variant, which was called "early repolarisation syndrome". This electrocardiographic (ECG) feature was usually described as an isolated pattern, without any coexistent conduction or myocardial abnormalities. A similar ECG pattern was observed in patients with severe hypothermia and different acute pathologic conditions.

In 1989 the group from Padua described an association between early repolarization, right bundle branch block (RBBB) of different degree, juvenile sudden death and right ventricular abnormalities, possible consistent with minor localised forms of right ventricular dysplasia/ cardiomyopathy [1]. Since then, a number of reports (summarized in table 1), have been published regarding this rare electrocardiographic (ECG) pattern and its clinical and diagnostic associations [1-20].

Despite identical or similar ECG patterns of the syndrome, two different pathogenesis are proposed. The first one, associates the RBBB+ST elevation with some organic ( and sometime genetically transmitted) heart disease of the right ventricle; the ECG pattern is linked to localized areas (septal and parietal) of the right ventricle in which there is a slowing and dispersion of depolarization. The second one ascribes the same electrocardiographic and clinical pattern to a different entity, namely an unknown idiopathic and functional electrical abnormality of some myocardial tissue (perhaps the M cells), producing dispersion of refractoriness and extreme anysotropic conduction. The purpose of this study is to examine the published cases of the disease, and to discuss the different pathogenesis proposed.

 

Definition of the term of "early repolarization"

In the absence of ischaemia, pericarditis, electrolytic abnormalities, long QT syndrome, "idiopathic " ST segment elevation has been longly recognized in clinical electrocardiography, since the initial description of Shipley et al. [21], on a four lead electrocardiogram. The most common pattern of this elevation with upward concavity has been named early repolarisation. The elevation, coincides with the the point on the ECG at which there is abrupt transition from the QRS complex to the ST segment (J point). It is usually recorded in the left precordial leads alone or simultaneously in the inferior leads; ST elevation restricted to the right precordial leads is unusual, according to the experience of Parisi et al. [22], who examined 49512 healthy males tracing.

According to Kambara, Wassemburg et al. [23,24] "early repolarization" include RS-T segment elevation of a minimum of 0.5 mm above baseline (greater than 2 mm in exceptional cases) in at least 2 limbs or precordial leads. Early repolarisation occurs in approximately 2.5% of adults and appear to be most commonly encountered in young black males. A similar electrocardiographic pattern is observed in the so called "vagotonia". RS-T elevation, which can be transient, may often persists for decades in many patients, and usually decreases with advancing age.

Intraventricular conduction disturbance namely right or left bundle branch block have been never proposed as a part of this entity, but minor QRS and T waves changes have been sometime described in early repolarization.

These QRS changes often associated to early repolarization, are characterized by nothching in the terminal portion of QRS at the J point, called J wave. Like early repolarization, the J wave is typically encountered in V3-V6 and in the inferior leads; sometime it is not a distinct wave but a slurred downstroke of the QRS complex (late delta wave).

In the recent literature the term J wave includes both the terminal QRS nothching and/or early repolarization [25 ]. As discussed before, however, early repolarization or J wave which is rarely seen in leads V1-V2 [21] should better named atypical J wave.

Atypical J wave is similar but distinct from incomplete RBBB as the terminal vector is not directed to the right but anteriorly and slightly leftward in the orizontal plane. In the ECG trace of these pts there is not a small slurred terminal vector in V6 and aVR, as it is expected in incomplete RBB. For these reasons, typical and atypical J wave are not the same electrocardiographic entity also if it has been recently hypothised that they might have the same electrogenesis but a different origin, namely typical J wave from the left ventricle and atypical J wave (R') from the right ventricle [26].

The T waves can be tall and peaked in early repolarisation; T wave inversion can be present as an unusual finding.

Typically RS-T changes normalise following isoproterenol infusion [27], increase following propanolol, and do not change after atropine.

The physiologic basis for early repolarization or J wave was considered the result of early onset of ventricular repolarization in a non-homogeneous manner which causes a difference of potential between myocardial areas resulting in ST elevation.The anomalous gradient between a site with faster recovery, underlying the exploring lead, and a site with slower recovery could be related to enhanced activity of the right sympathetic nerves which can be normalised by beta adrenergic stimulation [27].

 

Historical notes and pathophysiology of early repolarization associated to diseases

The J wave was firstly published in 1938 by Tomaszewski et al. [28] obtained in a man exposed to severe hypothermia. Osborn et al. [29] observed that all but one the hypothermic animals that developed ventricular fibrillation had J waves. J wave (particularly the atypical pattern), was further observed in patient with subarachnoid haemorrhage, brain injury, brain death, right radical neck surgery with destruction of sympathetic nerve fibres, and during resuscitation from cardiac arrest [10,25].

The recent elegant experimental observations of Yan and Antzelevitch [26] have tried to clarify part of this problem. They started from the old clinical observations that in severely hypothermic or hypercalcemic mammalians the ECG is characterized by J deflection. In animals the J wave is commonly observed under baseline conditions and is greatly amplified under hypothermic conditions. This author demonstrated in a canine model, that heterogeneous distribution of an Ito-mediated spike-and dome morphology of the action potential across the ventricular wall underlies the manifestation of the electrocardiographic J wave. A prominent Ito is the responsible for the relatively large phase 1 and the characteristic spike-and-dome configuration of the epicardial action potential. The absence of prominent notch in the endocardial action potential is correlated with a much smaller Ito. Cells in the M region may contribute to the J wave. The presence of a prominent potential notch in the epicardium but not endocardium is shown to provide a voltage gradient that manifest as a J wave or elevated J point at the R-ST junction of the ECG.

Antzelevich has demonstrated a highly significant correlation between the amplitude of the epicardial action potential notch and that of the J wave recorded during intervention that alter the appearance of the electrocardiographic J wave, including hypothermia, premature stimulation, and block of Ito by 4 aminopyridine. Ventricular activation from endocardium to epicardium, with epicardium activated last, was a prerequisite for the appearance of the J wave. This sequence permits the establishment of a voltage gradient of the early phases of the action potential after activation (i.e., the QRS) is complete.

The spike-and dome morphology of the right ventricular action potentials are more accentuated than that of the left ventricular epicardium. Despite the larger notch, because of the thinner ventricular wall and a briefer activation time, the right ventricular epicardial action potential notch occurs during the QRS and is obscured. This explain why the J wave is manifested (in animal models) in leads which mainly explore the left ventricle.

The presence of a prominent J wave has been shown to predispose canine ventricular epicardium to all-or-none repolarization and phase 2 re-entry. Under pathologic (not functional) conditions the action potentials plateau (dome) is abolished at some epicardial sites (especially of the right ventricle), causing a marked dispersion of repolarization. Loss of the plateau in epicardium but not endocardium causes elevation of the ST segment or early repolarization syndrome. The appearance of ST-segment elevation only in the right precordial leads is consistent with a loss of the action potential in right but not left ventricular epicardium. Loss of the dome can be accentuated by vagal manoeuvres or class 1 antiarrhythmic drugs, whereas b-adenergic agonist can restore the dome. Propagation of the the action potentials dome from sites at which it is maintained to sites where is abolished can cause local reexcitation (phase 2 re-entry), and produce ventricular arrhythmias.

 

 

Definition of the syndrome of aborted sudden death, right bundle branch bloch and early repolarization

This syndrome was described in detail in 1989 from the group in Padua [1], but became popular after the paper by Brugada and Brugada [3] who claimed in 1992 the originality of their "distinct" (not first) observation. In the following years, the published papers on this subjects, insisted sometime on the concept of two "identical but different" syndromes, the one described in Padua associated with an organic heart disease [1,5,7,9,11,14,15,19,20], and the second one associated with a functional disorder [2-4,6,8,10,12,13,16-18]. Marcus [30] and Sheinman [31], have recently expressed the opinion that a clear distinction between the two syndromes is difficult to prove.

There are some typical features of the syndrome, according to our experience and to the literature:

-A familial history of sudden death or similar ECG patterns in members of the same family are not unusual. An autosomal dominant inheritance with different expression seems to be involved [15].

-Aborted sudden death is often the first symptoms, but syncope is not so rare in the clinical history. Few patients (pts) up to now, have been recognized as having an asymptomatic form of the syndrome, and some had a late major clinical event [5,15,17,18].

-The syndrome is usually identified in the second and third decade, but infant and aged cases have been described [3-5,15]. The patients do not shows any cardiac impairment: cardiomegaly is not present and no previous illness possible leading to a cardiac disease were reported. Premature ventricular contractions, sometime polymorphic, are not routinely seen at Holter monitoring.

-Aborted sudden death do not significantly occurs during effort or stressfull situations. Only in occasional cases, a parasympathetic or sympathetic imbalance was proposed [8,10,16]

-The ECG patterns in different patients are similar and include an ST elevation usually associated with some right ventricular conduction disturbance, namely a complete or incomplete RBBB, or an atypical J wave (see before). The degree of RBBB and of ST elevation varies in selected cases over the time, and may be enhanced by pharmacological interventions [17]. R-ST elevation has howeverer been reported to be prominent only in few observations before and after the episode of aborted sudden death [11].

According to epidemiological data, the RBBB-ST pattern is a rare abnormality in asymptomatic pts, with an incidence of 0.63% in 10420 adults over 35 years [32]. In cardiac pts, it may be occasionally seen in pts with anteroseptal myocardial infarction, particularly when high precordial leads are recorded [14].

It has been proposed that also cases with an isolated ST segment elevation and malignant ventricular arrhythmias belongs to the syndrome [11,19,20]. In these cases, pharmacological interventions [17] or the recording of high precordial leads may show the typical pattern [14 ].

-Late potentials study can be positive.

-The electrical abnormality at the time of the resuscitation is ventricular fibrillation (VF); but polymorphic ventricular tachycardia can often be the preceeding ECG event [2,6,10,14]. Occasionally a monomorphic ventricular tachycardia of left bundle branch block morphology has been observed [16,19]. During further investigations, the pts have no spontaneous ventricular arrhythmias apart from isolated and non sustained premature ventricular contractions. During electrophysiologic study, a polymorphic ventricular tachycardia and or a VF is usually inducible. HV interval can be prolonged, usually in the pts with RBBB sometime associated with left axis deviation and prolonged PR interval [1,3,15,16]. A late QRS depolarization has been recorded at the outflow tract of the right ventricle in temporal relation with the ST segment elevation [33].

-Antiarrhythmic therapy is mandatory in these patients. Amiodaron and beta Blockers have been mostly used, but have been unsuccessful in some cases. An implantable defibrillator is becoming the first-choiche therapy with good results [2,4,10,16,17]

Pathogenesis:

In our first case affected by the syndrome and submitted to detailed necropsy, right ventricular dysplasia /cardiomyopathy has been documented [1,15]. Additional preliminary necropsy reports on similar cases have been recently presented [20].

This pt (n 3 of figure 1), had the first episode of ventricular fibrillation at the age of 24 years. His ECG showed firsts degree A-V block, left axis deviation, incomplete right bundle branch block, ST segmente elevation in the precordial leads (in a later trace, an increased ST elevation and inverted T waves were present in V1-V3 [15]). He had an HV interval of 70 msec. He died 5 years later, of a new episode of ventricular fibrillation. The heart weight was 350 gm; the left ventrice and the coronary arteries were normal. The right ventricle was enlarged (with preserved wall thickness), with marked dilatation of the pulmonary infundibulum; interstitial fibrosis and remarkable myocardial atrophy with transmural fatty replacement replacement of the free wall, the infundibulum and the moderator band. Results of histologic examination of the specialized atrioventricular junction showed remarkable fibrosis of the bifurcating bundle and proximal bundle branches. Considering the ECG disturbance, the prolonged HV interval, and the pathological results, we [15] suggested the presence of a double ventricular conduction defect, one in the septal area (responsible for the prolonged HV interval), and a second one at a localized right parietal site. This second delay, previously documented in similar patients affected by right ventricular dysplasia/cardiomyopathy, by epicardial mapping [34], can be further demonstrated by late potentials studies and by the direct recording during intracavitary study, of right ventricular depolarization electrical activity at the time of the abnormal ST segment [15,33,35]. This marked dispersion of ventricular activation times is likely to predispose to ventricular arrhythmias.

Apart from this necropsy evidence of a cardiac disease, more patients with the syndrome have been identified as having some concealed structural heart abnormality, particularly of the right ventricle [1,5,7,9,11,14,15,19,20]. The proposed diagnosis derived from 2D echo, angiography, bioptic studies, of both the left and right heart. Further data has come from the family study, the signal-averaged-ECG and the electrophysiologic recordings, the magnetic resonance imaging; in the near future the genetic analysis is expected to provide further informations.

The "distinct" syndrome later proposed lately [3] does much differ from our original description, apart from the absence of any cardiac disease in Brugada's patients, according to His investigational results. The number of patients with this "distinct" disorder, subsequently published, is not well definited because it is not clear if some of the patients described in Their registry [17] have also been described in other papers [2-4,6,8,10,12,13,16-18].

Brugada, while identifying a functional disorder, has lacked details regarding echocardiography, late potentials study, angiography, biopsy, magnetic resonance imaging, and necropsy examination in the 6 pts who died suddenly [3,17]. He could particularly not explain, why four of the eight patients in the first serie had a prolonged HV interval, which strongly suggested a structural disease at least of the His-Purkinje system.

The hypothesis that a functional cardiac electric disorder can lead to a devastating clinical event like sudden death, is supported in His opinion by:

-the conduction disturbance varies over the time in some patients, going from a absent to an increased degree of the right bundle branch block and ST segment elevation. On this base Brugada has also hypothised that in some patients affected by "idiopathic" ventricular fibrillation and with a normal recorded electrocardiogram, a concealed form of this disease may occur [17]. Some Asian authors have seen in this hypothesis a possible explanation for some cases of "nocturnal sudden death", with apparently normal ECG [11].

-Different pharmacological and pacing interventions can modify the electrocardiographic pattern.

Bjerregard et al. [10] noticed an enhancement of the wave during faster rates, suggesting a role for the autonomic nervous system. Recently Mijazaki et al. [16] in 4 pts with atypical J wave, noticed that ST segment elevation was augmented by stimulation of alpha-adrenoceptors or muscarinic receptors or by class 1A drugs, but was mitigated by beta-adrenoceptor stimulation or alpha-adrenoceptor blockade. MIBG imaging was negative in these pts. This drove to exclude a significant role for the autonomic system apart from an important modulation activity.

Ajmaline and procainamide can reproduce the typical ECG pattern in patients with a transient or concealed form of the electrical abnormality [17].

-The polymorphic characteristic of the ventricular arrhythmias and their fast cycle length suggest functional re-entry rather than a single re-entrant loop with a changing exit point. The re-entry can be easily triggered by spontaneous or induced premature beats. The underlying pathophysiology abnormality proposed by Brugada [3] was either marked dispersion of refractoriness of cardiac tissue or extreme anisotropic conduction properties of the conduction system and the ventricular muscle. Recently Brugada has speculated the role of a functional abnormality of the M cells in this disease, which could cause an abnormal depolarization- repolarization [17].

Conclusion

In our opinion [1,15,20], supported by others [5,7,9,11,14,15,19,30,31], the syndrome of sudden death, RBBB and ST segment elevation recognises a pathological structural basis in the right ventricle, possibly consistent with a localized form of right ventricular cardiomyopathy.

From the ECG point of view, three pattern can be recognised: 1) Typical complete or incomplete RBBB + ST elevation; 2) Atypical J wave in the precordial leads; 3) Isolated ST elevation in the precordial leads. The clinical and investigational data are similar in the 3 groups.

Right ventricular dysplasia/cardiomyopathy [36,37] is often an autosomic dominant ereditary condition [38], characterised by atrophy and fibro-adipose substituion of the right and less of the left ventricle. Its pathologic and clinical presentation is extremely polymorphic, going from extremely severe involvement of the right and of sometime the left ventricle, to asymptomatic structural abnormalities very difficult to adcertain, but sharing a common problem: a high prevalence of different ventricular arrhythmias and sometime sudden death [36-38]. The disease was always existed, but only after the work of Marcus and Fontaine [36], it was worldwide (sooner or later) recognised. After that report, cases of sudden death and many ventricular arrhythmias, previously retained idiopathic and functional, have recognized their origin from some right ventricular pathology [39-42], always followed by intensive debate and sceticism.

These evidences of a pathologic substrate for idiopathic sudden death and for idiopathic arrhythmias, derived from a careful analysis of old and often forgotten clinical clues like family history, detailed examination of the ECG tracing particularly of the pseudo-normal patterns, accurate analysis and description of the results of invasive and non invasive investigations, correct utylisation of the results of the experimental works, continuous debate and self-criticism. The valorisation of minor abnormalities, was a prerequisite for such analysis, and the researcher's mind was not obscured by what was commonly retained the only true medical knowledege.

The utylisation of these criteria has led to the identification of the syndrome of RBB+ST segment elevation characterised by structural and electrical herat abnormalities. This is perhaps only a little contribution to the prevention of some cases of sudden death but we, and all the scientists who gave some contribution to the syndrome in different countries, expect that the patho-electrogenetic hypothesis, and the diagnostic and therapeutic approach described in this article will further ameliorate.

 

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    10. -Bjerregaard P, Gussak I, Kotar S, Gessler JE, Janosik D. Recurrent syncope in a patient with prominent J wave. Am Heart J 1994;127:1426-30
    11. -Tada H, Aihara N, Ohe T, Yutani C, Shimizu W, Kurita T, Kamakura s, Shimomura K. New insight in idiopathic ventricular fibrillation patients with right precordial ST segment elevation. Circulation 1994;90:1511 (abstract)
    12. -Ferracci A, Fromer M, Schlapfer J, Pruvot E, Kappemberger L. Fibrillation ventriculaire primitive et recidive precoce; à propos d'un cas associant bloc de branche droit et sus-décalage persistant du segment ST. Arch Mal Coeur 1994;87:1359-1362
    13. -Nademanee K, Veerakul G, Nimmanit S, Tungsanga K, Chaowakul V, Malasit P. Right bundle branch block and ST segmente elevation, an arrhythmohgenic marker for sudden unexpected death syndrome in young Thai men. Circulation 1995;92:1596 (abstract)
    14. -Naccarella F, Mezzetti M, Palmieri M, Barbato G, Medda M, Di Niro MR, Cavallari F, Masotti A, Bracchetti D, Nanni G, Rimondini R. Analysis of the ECG pattern "incomplete right bundle branch block and ST elevation in V1 V3 in different clinical subsets. A primary electrical disease or an early high right anteroseptal involvement as in right ventricular dysplasia-cardiomyopathy? Preliminary results. New Trends Arrhythmias 1996;9:405-8
    15. -Corrado D, Nava A, Buja GF, Martini B, Fasoli G, Oselladore L, Turrini P, Thiene G. Familial cardiomyopathy underlies syndrome of right bundle branch block, ST segment elevation and sudden death. J Am Coll Cardiol 1996;27:443-8
    16. -MiYazaki T, Mitamura H, Miyoshi S, . Autonomic and antiarrhythmic drug modulation on of the ST segment elevation in patients with Brugada Syndrome. J Am Coll Cardiol 1996;27:1061-70
    17. -Brugada J, Brugada P. What to do in patients with no structural heart disease and sudden arrhythmic death? Am J Cardiol 1996;78(suppl 5a):69-75
    18. -Gussak I, Bijerregaard P, Chaitman B. ECG phenomenon called J wave: from hypothermia to Brugada syndrome. European Journal of Cardiac Pacing and Electrophysiology 1996;6:130 (abstract)
    19. -Sheinman MM. Right bundle branch block and ST Elevation is not a distinct syndrome identifying patients at risk for sudden cardiac death. European Journal of Cardiac Pacing and Electrophysiology 1996;6:7 (abstract)
    20. -Corrado D, Basso C, Buja GF, Nava A, Thiene G Pathologic substrates of right bundle branch block, persistent right precordial ST segment elevation, and sudden death in young people. EUR J C P E 1996;6:36 (abstract).
    21. -Shipley RA, Hallaran WR. The four lead electrocardiogram in 200 normal men and women. Am Heart J 1936;325-345
    22. -Parisi A, Beckman C, Lancaster M. The spectrum of ST segment elevation in the electrocardiogram of healthy adult men. J Electrocardiology 1971;4:137-44
    23. -Kambara H, Phillips J. Long-term evaluation early repolarization syndrome (normal variant RS-T segment elevation). Am J Cardiol 1976;38:157-61
    24. -Wassemburg RM, Alt WJ, Lloyd C. The normal RS-T segment elevation variant. Am J Cardiol 1961;8:184-192
    25. -Gussak I, Bjerregaard P, Egan T, Chaitman B. ECG phenomenon called the J wave. Journal of Electrocardiology. 1995;28:49-58
    26. -Yan GX, Antzelevitch C. Cellular basis for the electrocardiographic J wave. Circulation 1996;93:372-9
    27. -Morace G, Padeletti L, Porciani M, Fantini F. Effect of isoproterenol on the "early repolarization " syndrome. Am Heart J 1979;97:343-7
    28. -Tomaszewski W. Changements electrocardiographiques observes ches un homme mort de froid. Arch Mal Coeur 1938;31:525-8
    29. -Osborn JJ. Experimental hypothermia: respiratory and blood pH changes in relation to cardiac function. Am J Physiol 1953;175:389-98
    30. -Marcus FI, Fontaine G. Arrhythmogenic right ventricular dysplasia/cardiomyopathy. PACE 1995;18:1298-1313
    31. -Sheinman M M. Is the Brugada syndrome a distinct clinical entity? J Cardiovascular Electrophysiology. In press
    32. -Namiki T, Ogura T, Kuwabara Y, Kobayashi S, Saito T, Masuda Y. Five-year mortality and clinical characteristics of adult subjects with right bundle branch block with ST elevation. Circulation 1995;92:1591 (abstract)
    33. -Nava A, Canciani B, Schiavinato ML, Martini B, Buja GF. La repolarisation precoce dans le precordiales droites: trouble de la conduction intraventriculaire droite? Correlations de l'electrocardiographie- vectorcardiographie avec l'electro- physiologie. Mises a Jour Cardiologiques 1988;17:157-9
    34. -Fontaine G, Frank R, Guiraudon G. Signification des troubles de conduction intraventriculaires observés dans la dysplasie aventriculaire droite arytmogene. Arch Mal Coeur 1984;77:872-9
    35. -Nava A, Canciani B, Buja GF, Martini B, Scognamiglio R, Daliento L, Oselladore L, Thiene G.. El electrocardiograma y el vectorcardiograma en la dysplasia arritmogénica del ventriculo derecho. Revista Latina de Cardiologia 1992;15:276-83
    36. -Marcus FI, Fontaine GH, Guiraudon G. Right Ventricular Dysplasia: A report of 26 Adult cases. Circulation 1982;65:384-397
    37. -Thiene G, Nava A, Corrado D, Rossi L, Pennelli N. Right ventricular cardiomyopathy and sudden death in young people. N Engl J Med 1988;318:129-133
    38. -Nava A, Thiene G, Canciani B, Scognamiglio R, Daliento L, Buja GF, Martini B, Stritoni P, Fasoli G. Familial occurrence of right ventricular dysplasia: a study involving nine families. J Am Coll Cardiol 1988;12:1222-8
    39. -Nava A, Scognamiglio R, Thiene G, Canciani B, Daliento L, Boffa GM, Stritoni P. A Polymorphic form of familial arrhythmogenic right ventricular dysplasia. Am J Cardiol 1987;59:1405-1409
    40. -Martini B, Nava A, Thiene G, Buja GF, Miraglia G, Scognamiglio R, Boffa GM, Daliento L. Accelerated idioventricular rhythm of infundibular origin in patients with a concealed form of arrhythmogenic right ventricular dysplasia. Br Heart J 1988;59:564-71
    41. -Martini B, Nava A, Thiene G, Buja GF, Canciani B, Miraglia G, Scognamiglio R, Daliento L, Dalla Volta S. Monomorphic repetitive rhythms originating from the right ventricular outflow tract in patients with minor forms of right ventricular cardiomyopathy. Intern J Cardiol 1990;27:211-21
    42. -Corrado D. Thiene G, Nava A, Rossi L., Pennelli N. Sudden death in young competitive athletes: clinico-pathologic correlations in 22 cases. Am J Med 1995;89:588-96

 

-Author

-Year

-N.cases

-[Reference]Angiography (right and left ventricle) or 2D echo or MRI

 

 

                   

Martini

1989

3

[1]

35/M

31/M

24/M

VF,PVC

VF,PVC

VF,PVC

yes

yes

yes

RBBB+ST

J wave+ST+LAD

IRBBB+ST+LAD

-

Pos

-

45

45

70

NSPVT/VF

PRR

SR

RVA

RVA

RVA

Fib

-

Fib Fat

SD

Asymp

SD

 

Amio.

Amio.

-

Aihara

1990

1

[2]

25/M

SPVT/VF,PVC

?

IRBBB+ST

?

?

VF

Negative

?

?

Procainamide

Brugada

1992

8

[3]

2/M

2/F

46/M

48/M

44/M

53/M

8/F

26/M

SPVT/VF,PVC

SPVT/VF,PVC

SPVT/VF,PVC

SPVT/VF,PVC

SPVT/VFPVC

SPVT/VF,PVC

SPVT/VF,AF

SPVT/VF,PVC

 

yes

yes

yes

no

no

yes

no

no

IRBBB+ST

RBBB+ST

RBBB+ST

J wave+ST

J wave+ST

RBBB+ST

J wave+ST

IRBBB+ST

-

-

-

-

-

-

-

-

 

70

-

80

40

45

65

35

60

NSPVT

-

SPVT/VF

SPVT/VF

NSPVT

NSPVT

SPVT/VF

SPVT/VF

Negative

-

Negative

Negative

Negative

Negative

Negative

Negative

 

-

-

-

-

Neg

Neg

Neg

Neg

 

Recur

SD

Asymp.

Asymp

Asymp

Asymp

Recur

Asymp

Am Dip PM

Am PM

-

BB Dip

ID

ID

Dig BB ID

Am ID

Proclemer

1993

1

[4]

65/M

VF

no

RBBB+ST

Pos

40

VF

Uncommon trabecular pattern

Neg

Recur

Am ID

Naccarella

1993

1

[5]

72/M

NONE

?

J wave+ST+LAD

?

?

?

?

?

?

?

Miyanuma

1993

2

[6]

47M

39/M

SPVT/VF,PVC

VF

?

IRBBB+ST

J wave + ST

-

Neg

?

-

SPVT/VF

Negative

Negative

Neg

Neg

 

SD

Asymp.

Dysopiramide

Dysopiramide

Sumiyoshi

1993

1

[7]

42/M

SPVT/VF

no

IRBBB+ST

-

normal

Neg

Moderately dilated RV and LV

LV Fib, RV not done

Asymp

BB, Mexiletine

Aizawa

1993

1

[8]

?

VF

?

IRBBB+ST

atypical J wave in V3-V5,

bradycardia dependent

?

normal

?

Neg

?

?

?

Wiesfeld

1994

1

[9]

36/M

VF,PVC

?

*IRBBB+ST

?

normal?

AF/AFL

Normal

Fib fat

?

?

Bjerregaard

1994

1

[10]

47/F

SPVT,PVC, Triplets

no

J wave+ST

Neg

normal

NSPVT

Neg

-

Asymp

BB ID

Tada

1994

9

[11]

All males

All VF

?

"Dynamic right precordial ST elevation"

?

)

?

5 had RVA

Neg in all

?

?

Ferracci

1994

1

[12 ]

36 M

VF

?

*IRBB+ST

Neg

normal

neg

Neg

Neg

SPVT/VF

ID

Nademanee

1995

9

[13]

?

all syncope or aborted SD

?

* RBBB+ST

(dynamic)

All Pos

?

NSPVT/ VF

Negative

?

2 SD

?

Naccarella

1996

6

[ 14]

18/M

53/M

65/M

45/F

29/F

35/M

VT/VF

VT/VF

NSVT

NSVT

SVT,PVC

SVT,PVC

YES

YES

YES

YES

YES

YES

*IRBB+ST+LAD

*IRBB+ST+LAD

*IRBB+ST

*RBBB+ST+LAD

*IRBB+ST+LAD

*IRBB+ST+LAD

?

?

?

?

?

?

?

?

?

?

?

^

?

?

?

?

?

?

RVA

RVA

RVA

RVA

RVA

RVA

-

-

Fib, Fat

Fib, Fat

Fib,Fat

Fb,Fat

?

?

?

?

?

?

?

?

?

?

?

?

Corrado

1996

7

[15]

 

 

 

?

?

?

?

?

?

?

None

None (palpit.)

None

None(palpit)

None

None

None

yes

yes

yes

yes

yes

yes

yes

J wave+ST

IRBBB+ST+LAD

IRBBB+ST+LAD

IRBBB +ST

IRBBB+ST

loc ST

J wave+ST

Pos

Pos

Neg

Pos

Neg

Neg

Pos

-

80

-

-

-

-

-

-

SMVT (LBBB)

-

-

-

-

-

RVA

RVA

-

RVA

-

-

RVA

-

Fib Fat

-

-

-

-

-

-

Palp

-

Palp

-

-

-

-

Amio

-

BB

-

-

-

Miyazaki

1996

4

[16]

29/M

47/M

41/M

38/M

SMVT (LBBB)

PVC

- (palpit)

VF

?

?

?

?

IRBBB+ST+LAD

J wave+ST

J wave+ST

J wave+ST

Pos

Neg

-

Neg

100

normal

normal

normal

SMVT,VF

VF

VF

-

Negative

Negative

Negative

Negative

Neg

Neg

-

Neg

Asymp

Asymp

Asymp

Recur

BB

Doxasozine

ID

ID Mexiletine

Brugada J

1996

47 (including 8 of ref. 3)

[17]

?

32 SPVTand or VF.

-15 asymptomatic

yes

*RBBB+ST

(transient in 14)

?

?

32/38 SPVT/VF

 

 

 

Negative

Non speciphic in 16

6 SD with 2 macroscopically normal autopsy (no details)

-22 ID + Amio/ BB

17 Amio/ BB/sotalol

 

Gussak

1996

4 (including 1 of ref .10)

[18]

?

-1 with VT/VF

-3 asymptomatic

?

*J wave

?

?

?

?

?

?

?

Sheinman

1996

4

[19]

?

All had SMVT (LBBB )

?

*2 RBBB+ST

*2 ST

?

?

All inducible VT

ARVC

?

?

?

Corrado

1996

11

[20]

All less than 35 years

All sudden death

?

*3 RBBB+ST

*8 ST

?

?

?

?

All ARVC at autopsy

All died suddenly

?

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

= Age at the time of the documented episode of aborted sudden death. F=female, M=male. * = ECG trace not published. ? =data not reported. - = not performed. Palp = palpitations. Syn = syncope. RBBB = right bundle branch block. IRBBB = incomplete right bundle branch block (intends r' pattern in V1 aVR with s' in V6). J wave=localized pattern of IRBBB+ST in precordial leads without r' in aVR and s' inV6 (atypical J wave). Pos = positive study. Neg = negative study. MRI = magnetic resonance imaging. LAD= left axis deviation. RV = right ventricle. LV = left ventricle. VT = ventricular tachycardia. NSVT= non sustained ventricular tachycardia. NSPVT = nonsustained polymorphic ventricular tachycardia. SPVT = sustained polymorphic ventricular tachycardia. SMVT = sustained monomorphic ventricular tachycardia. VF = ventricular fibrillation. PVC =premature ventricualr contractions, PPVC = polymorphic ventricular contractions. PRR = polimorphic repetitive response. SR = single response. AF/AFL = atrial fibrillation/flutter. LBBB = left bundle branch block QRS morphology of the ventricular arrhythmia. RVA = right ventricular abnormalities. Fib = fibrosis. Fat = fatty replacement. ARVC = arrhythmogenic right ventricular cardiomyopathy. SD = sudde death. Asymp = asymptomatic. Am = amiodaron, BB = beta-blockers. Dip = diphenylhydantoin. Dig = digitalis. PM = VVI permanent pace-maker. ID = implantable defibrillator

 

 

 

 

 

 

 

 

 

 

 

 

 

 

COMPLETE REFERENCE ON THE

SYNDROME OF RIGHT BUNDLE BRANCH BLOCK, ST SEGMENT ELEVATION

AND SUDDEN DEATH

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