Case 4 -
Sudden Death in a 35 Year Old Man with First Degree AV Block
Right Bundle Branch Block and ST Segment Elevation in Right Precordial Leads
University of Padua Medical School
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A 35-year old truck driver had been admitted to the hospital at age 30 years for evaluation of
recurrent syncopal episodes. He experienced an in-hospital sudden cardiac arrest due to recorded
ventricular fibrillation and was successfully resuscrequired direct current cardioversion at 300 J.
Results of a clinical examination were normal. Serial 12-lead ECGs showed sinus rhythm, first-degree
atrioventricular (AV) block (PR interval 220 ms), right bundle branch block with left axis deviation, ST
segment elevation and inverted T waves in the right precordial leads (Fig. 1). Chest roentgenogram
showed a normal cardiothoracic ratio; the results of baseline hematologic and biochemical studies were
within normal limits. Exercise stress testing and 24-h Holter ambulatory ECG monitoring showed no
arrhythmias. Cardiac catheterisation revealed normal cardiac pressure, as well as normal findings on
left ventricular and coronary angiography and ergonovine testing. Right ventricular angiography was not
performed. Intracardiac electrophysiologic recordings revealed a “borderline” HV interval
(70 ms); programmed ventricular stimulation was not performed. The patient was given bet-adrenergic
blocking therapy and his clinical course was uneventful until he died suddenly at rest 5 years later.
Case 4 - Figure 1 - 12 lead ECG showing sinus rhythm, first-degree atrioventricular (AV) block (PR interval 220 ms), right bundle branch block with left axis deviation, ST segment elevation and inverted T waves in the right precordial leads
Case 4 - Figure 2 - Panoramic full thickness section of the RV wall at the level of moderator band showing transmural fatty infiltration of the myocardium, in the absence of replacement fibrosis
Case 4 - Figure 3 - Serial histologic section of the specialized conduction system showing severe fibrosis of the bifurcating His bundle with sclerotic interruption of the right bundle branch
Postmortem examination revealed a heart weight of 350 g. The coronary
arteries were normal and there was no evidence of recent or healed myocardial infarction. All cardiac
valves were normal. The right ventricle was moderately enlarged with dilatation of the pulmonary
infundibulum. Despite preserved right ventricular wall thickness (4 to 5 mm), there was significant
myocardial fatty infiltration in the right ventricular anterolateral wall.
examination of the right ventricular myocardium showed remarkable transmural myocardial fibers
dissociation by fatty infiltration and slight interstitial fibrosis, in the absence of wall thinning,
inflammatory infiltrates and myocyte degenerative changes (Fig. 2). Study of the specialized conduction
system showed normal findings in the sinoatrial node, crista terminalis, atrionodal approaches, AV node
and penetrating AV bundle. Conversely, there was marked fibrosis of the bifurcating His and branch
bundles with fibrous interruption of the proximal right bundle branch (Fig. 3).
Pedigree analysis revealed that 50%
of the investigated family members exhibited some degree of right bundle branch block or ST segment
elevation, or both, in the right precordial leads, as to suggest a pattern of inheritance compatible with
an autosomal dominant pattern with variable expression.
genetic investigation in the affected family members disclosed a sodium channel gene mutation
(SCN5A) probably accounting for both Brugada syndrome and Lenegre disease phenotypic expression (courtesy
of Prof. Priori and Prof. Danieli).
|I. ||Arrhythmogenic right ventricular cardiomyopathy (ARVC)|
|II. ||Fatty infiltration of the right ventricle|
|III.||Conduction system disease affecting the bundle branches (Lenegre disease)|
|IV. ||Brugada syndrome (idiopathic VF)|
Brugada syndrome with specialized conduction system pathology (Lenegre disease)
Sudden cardiac death usually occurs in the setting of structural disease (“mors cum materia”). The substrate is frequently identified at naked eye
examination of the cardiac specimen, followed by a thorough histological investigation. Gross and
histologic features in our case were first indicative for fatty infiltration
of the right ventricle, however fat replacement of the right ventricle is not sufficient for the
diagnosis of ARVC (either fatty or fibro-fatty types) . Massive fatty infiltration of the right
ventricle without any evidence of fibrosis and myocyte degeneration should be considered as a separate
clinico-pathologic entity from ARVC .
In nearly 10% of cases, sudden cardiac death may appear as “mors sine
materia” in so far as even a skilled morphologic examination fails to detect structural
abnormalities and the heart is apparently normal . This condition was known as
“idiopathic” ventricular fibrillation. A thorough histologic investigation of the working
myocardium as well as of the specialized conduction system should be carried out before ruling out a
diagnosis of normal heart.
The underlying diseases are mostly heredo-familiar and the recent development of molecular genetics
demonstrated that we are dealing with abnormalities which affect the molecular mechanisms of electrical
cardiac stability and electro-mechanical coupling. A series of clinical entities, known as
channellopaties, have been discovered in the last decades and have been related to gene defects which
account for the great majority of so called idiopathic ventricular fibrillation. They include long QT
syndrome, Brugada syndrome, and effort-induced polymorphic ventricular tachicardia
A part from the channellopathies, sudden cardiac death may occur in the setting of a grossly and
histologically normal heart, since the abnormality may reside in the cardiac conduction system (AV node,
bundle branches -Lenegre disease-, and anomalous pathways) 10).
Noteworthy, among the gene defects discovered to account for so-called “idiopathic”
ventricular fibrillation, the sodium channel gene mutation (SCN5A) has been implied not only in the long
QT syndrome -LQT3-, but also in Brugada syndrome and more recently it has been demonstrated to underlie
cardiac conduction defects with progressive disease of specialized AV junction and AV block
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