[SCD-FORUM] 24E RE: CLBBB. Dr. Perez Riera

[SCD Symposium]

Dear Dr Jorge Ruiz Alais  here answer Andrés Ricardo Pérez Riera  
ffrom São Paulo Brazil.
In apparently healthy men the Manitoba prospective population follow- 
Up study (1948 to 2004) showed that newly developed complete left  
bundle branch block (CLBBB) was a highly significant short-term risk  
to sudden unexpected cardiac death that diminished with time (1).
Cardiac resynchronization therapy (CRT) has significant positive  
effects on the quality of life, enables patients to cope more  
efficiently with cardiopulmonary stress and leads to a reduction of  
total mortality in patients suffering from congestive HF NYHA classes  
III and IV, reduced LV function and CLBBB with a QRSd > 150 ms.  
Prolongation of QRSd > or =120 ms occurs in 14% to 47% of HF  
patients. LBBB is far more common than RBBB. Left-sided  
intraventricular conduction delay is associated with more advanced  
myocardial disease, worse LV function, poorer prognosis, and a higher  
all-cause mortality rate compared with narrow QRS complex.   In a  
large number of patients suited for CRT, an additional defibrillator  
function seems to work out well concerning an additional prognostic  
improvement by means of reducing SCD. Due to partially contradictory  
study outcomes, it still remains to be discussed whether all patients  
suited for CRT really need an ICD (2). In ICD patients with HF, a  
wide underlying QRS complex more than doubles the cardiac mortality  
compared with a narrow QRS complex. There is a high incidence of an  
elevated defibrillation threshold at the time of ICD implantation in  
patients with QRS > or =200 ms. Mechanical LV dyssynchrony  
potentially treatable by ventricular resynchronization occurs in  
about 70% of HF patients with left-sided intraventricular conduction  
delay, a fact that would explain the lack of therapeutic response in  
about 30% of patients subjected to ventricular resynchronization  
according to standard criteria relying on QRS duration. The duration  
of the basal QRS complex does not reliably predict the clinical  
response to ventricular resynchronization, and QRS narrowing after  
cardiac resynchronization therapy does not correlate with hemodynamic  
and clinical improvement. Mechanical LV dyssynchrony is best shown by  
evolving echocardiographic techniques (predominantly tissue Doppler  
imaging) currently in the process of standardization (3).
The presence of BBB is strongly associated with future high-degree  
atrioventricular block that was more pronounced for LBBB. Men with  
LBBB have a substantially increased risk of coronary death, mainly  
due to SCD outside the hospital setting (4).
Lènegre disease is the eponym of "idiopathic" progressive disease of  
the His-Purkinje system. It is also knows as Progressive Cardiac  
Conduction Defect (PCCD). The disease has been identified as an  
entity that affect  the sodium fast channel  (channelopathy entity)  
occasioned by mutation in the SCN5A gene. It is an allelic of Brugada  
disease with a different phenotypic expression. The same missence  
mutation in the SCN5A gene can cause both phenotypes: Brugada and  
Lènegre disease.
So, we now ask for scientific community: why Lènegre has disease  
category and Brugada entity has not?. Is it certain? Both entities,  
called Progressive Cardiac Conduction Defects (PCCD), are grouped  
together as primary conduction diseases (Lev-Lenègre). Both Lenègre  
disease-known as "primary" PCCD (5)-as well as the secondary mechanic  
lesion-sclerosis of the left "cardiac skeleton" or Lev disease (6)- 
usually cause LBBB or RBBB, frequently associated with divisional  
blocks.

Occasionally, they develop into more advanced degrees of block with a  
potential to cause SCD due to total AV block, to the extent that they  
represent the most important cause of  pacemaker implantation in the  
first world: 0.15 per 1,000 inhabitants a year.

The same mutation in novel single SCN5A missense mutation can lead  
either to Brugada syndrome or to an PCCD. Modifier gene(s) may  
influence the phenotypic consequences of a SCN5A mutation. A G-to-T  
mutation at position 4372 was identified by direct sequencing and was  
predicted to change a glycine for an arginine (G1406R) between the  
DIII-S5 and DIII-S6 domain of the Na+ channel protein (7).

Trimetazidine (TMZ) Vartel  a clinically effective antianginal agent  
with no negative inotropic or vascular properties, acts by optimizing  
cardiac energy metabolism through inhibition of free faty acid  
oxidation, shifting substrate utilization from fatty acids to  
glucose. long-term trimetazidine improves functional class and LV  
function in patients with HF. This benefit contrasts with the natural  
history of the disease, as shown by the decrease of EF in patients on  
standard HF therapy alone. Recently, results have demonstrated that  
trimetazidine improves radial artery endothelium-dependent relaxation  
related to its antioxidant properties. Similarly, exercise training  
has been demonstrated to improve diastolic filling and systolic  
function in patients with ischemic cardiomyopathy, in relation to  
enhanced perfusion and contractility of dysfunctional myocardium.  
Patients with viable myocardium, in theory, should have the greatest  
benefits because trimetazidine improves contractility of  
dysfunctional hibernating/stunned myocardium, whereas exercise has  
documented efficacy in improving endothelial vasomotor response of  
coronary arteries, stimulating coronary collateral circulation and  
small vessel growth, improving LV function, and increasing functional  
capacity.

References
1)       Cuddy TE, Tate RB. Sudden unexpected cardiac death as a  
function of time since the detection of electrocardiographic and  
clinical risk factors in apparently healthy men: the Manitoba Follow- 
Up Study, 1948 to 2004. Can J Cardiol. 2006;22:205-11.
2)       Volkmann H, Bergmann C, Walter M.Cardiac resynchronization  
therapy: who is suitable? Who requires an additional ICD as a backup?  
Z Kardiol. 2005; 94:60-64.
3)       Kashani A, Barold SS. Significance of QRS complex duration  
in patients with heart failure. J Am Coll Cardiol. 2005;46:2183-92.
4)       Eriksson P, Wilhelmsen L, Rosengren A.Bundle-branch block in  
middle-aged men: risk of complications and death over 28 years. The  
Primary Prevention Study in Goteborg, Sweden. Eur Heart J.  
2005;26:2222-3.
5)       Lenègre J.The pathology of complete atrioventricular block.  
Progr Cardiovasc Dis  1964; 6:317-323.
6)       Lev M. Anatomic basis of atrioventricular block. Am J Med  
196437:742.
7)       Kyndt F, Probst V, Potet F, et. al. Novel SCN5A Mutation  
Leading Either to Isolated Cardiac Conduction Defect or Brugada  
Syndrome in  a Large French Family.  Circulation 2001; 104: 3081-3086

All the best

Andrés Ricardo Pérez Riera
Chief of Electro-Vectocardiology Sector of the Discipline of Cardiology,
ABC Faculty of Medicine (FMABC), Foundation of ABC (FUABC)
- Santo André -  São Paulo - Brazil.
Rua Sebastião Afonso  885 - Zip Code: 044417-100- Jardim Miriam  S.P  
Brazil-

>
> Dear friends,
> Congratulations on such a novel and scientific symposium on heart
> pathologies, for I am personally quite surprised with the advanced
> progresses that help to clarify and understand lots of pathologies
> still unknown to many colleagues. By the way, I would like to know
> about the newest advancements about complete left bundle branch block
> of his bundle; if this may actually be a pathology that may cause
> sudden death; clarify its etiology, prognosis, proper management,
> what other complications it may have, and if possible, whether there
> is some innovative treatment to endure this condition. I would also
> like to know what is the experience regarding the cardiac ischemia
> treatment with vastarel (trimetazidine dichlorhydrate).
> Thank you very much for your consideration to this message.
> I remain waiting for your kind response,
>
> JORGE RUIZ ALAIS


--
Dr. Sergio Dubner
President of Scientific Committee

Dr. Edgardo Schapachnik
President of Steering Committee




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