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

[SCD Symposium]

24E RE：CLBBB.－ Perez Riera 医生
尊敬的Jorge Ruiz Alais医生给予来自巴西圣保罗Andrés  
Ricardo Pérez Riera的回答。
Manitoba前瞻性健康人群随访研究(1948 至 2004)中发现新 
近进展的完全性左束支传导阻滞（CLBBB）是短期内无 
预料的心脏猝死的高危因素（1）。心脏再同步治疗 
（CRT）可显著改善生活质量，可以使患者更有效地承 
受心肺压力，并且可减少NYHA III 和IV级心衰患者的总 
死亡率，降低左室功能和QRSd > 150 ms的CLBBB。心衰患者 
中14% 到47% 会出现QRSd 延长≥120 ms。LBBB比RBBB多见，与 
窄QRS波相比，左侧心室内传导延迟和心肌疾病进展、 
左室功能降低、预后不良和全因死亡率增高相关性更 
强。在适于CRT的大量患者中，额外的除颤器功能通过 
减少SCD的发生而很好的改善预后。由于部分研究结果 
有争议，是否所有适合CRT的患者需要ICD尚待进一步的 
讨论（2）。在植入ICD的心衰患者中，宽QRS波心源性 
死亡的发生率是窄QRS波患者的两倍多。QRS波≥200 ms的 
患者在ICD植入时除颤阈值更高。70％左室内传导延迟 
的心衰患者中可通过心室再同步化治疗机械性左室失 
同步，而剩下的30％对心室再同步化治疗无反应的患 
者按照QRS波时程标准进行心室同步化治疗。QRS波时程 
不能可靠预测对心室同步化治疗的反应性，而且心脏 
再同步化治疗后QRS的变窄并不改善血流动力学和临床 
症状。目前，左室机械性失同步的标准评价中，心超 
（尤其是组织多普勒影像）中显示最好（3）。
束支传导阻滞伴高度房室传导阻滞大多为LBBB。LBBB患 
者发生冠脉死亡的危险增加，主要由于院外发生SCD 
（4）。

Lenegre疾病是指特发性进行性希氏－蒲肯野系统疾 
病。它也被称为进行性心脏传导功能缺陷（PCCD）。 
该疾病被认为是由于SCN5A基因突变影响了快钠通道所 
致，它也是Brugada的一对等位基因，但表型表达不同。 
SCN5A基因突变可引起两种表型：Brugada病和Lenegre病。

我们想问一下科委会：为什么Lenegre有分类而Brugada却 
没有？此分类确定吗？这两类进行性心脏传导功能缺 
陷（PCCD）被统称为原发性传导疾病（Lev－Lenegre）。 
Lenegre病—即原发性PCCD（5）和左侧“心脏骨骼”的继 
发性机械损伤－硬化或Lev病（6）—可引起LBBB或RBBB， 
通常和分区阻滞相关。
偶尔，他们可以进一步加重阻滞程度致完全性房室传 
导阻滞而引起SCD，这是第一世界植入起搏器最重要的 
原因：每年每1，000个居民中约为0.15.
SCN5A相似位点的单一缺失突变可引起Brugada综合征，或 
者PCCD。修饰基因可能影响到SCN5A突变表型。通过直接 
测序法确定为4372位点上G→T突变，预示着在钠通道蛋 
白DIII-S5 和DIII-S6区域间的甘氨酸转变为精氨酸(G1406R) 
（7）。

曲美他嗪（TMZ）是临床有效的抗心绞痛药物，没有负 
性肌力和血管作用，通过利抑制游离脂肪酸氧化作 
用、改变脂肪酸转化为葡萄糖时的底物利用，而优化 
心脏能量代谢。长期使用曲美他嗪可改善心衰患者心 
功能级别和左室功能。该益处可对抗疾病的自然病 
程，因为仅用标准治疗的心衰患者EF降低。最近，结 
果显示曲美他嗪因其抗氧化作用可改善桡动脉内皮依 
赖性松弛作用。类似的，运动锻炼可改善缺血性心肌 
病患者舒张充盈和收缩功能，与提高功能障碍心肌的 
灌注和收缩性相关。心肌有活力的患者，理论上，应 
该获益最大，因为曲美他嗪可改善功能障碍的冬眠/ 
顿抑心肌的收缩性，而运动锻炼已证实可有效改善冠 
脉内皮血管的舒缩反应，刺激冠状侧支循环和小血管 
生长，改善LV功能，增加有效循环血容量。
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-

胡文瑛译 王玲洁校
24E RE: CLBBB.－ Dr. Perez Riera

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-
--
Dr. Sergio Dubner
President of Scientific Committee

Dr. Edgardo Schapachnik
President of Steering Committee

>
> 2s ：完全性左束支传导阻滞－ Ruiz Alais 医师
>
> 亲爱的朋友：
>
> 祝贺这一心脏病理学方面新颖的科学论坛的召开。此
> 次论坛的先进性我个人深感称奇，它有助于阐明和理
> 解诸多同道们不知晓的多种病理机制。同时，我想知
> 道有关His束完全性左束支传导阻滞的最新进展；它是
> 否确实是引起猝死的病理机制；它能否阐明病因、预
> 后、正确治疗以及可能存在的其他并发症，如果可能
> 的话，是否有一些创新性治疗措施能改善此种状态，
> 我还想了解一下vastarel（三甲基苄嗪二氯丙醇）治疗
> 心肌缺血的应用经验。
>
> 非常感谢您关注此信息，切盼回音。
>
> JORGE RUIZ ALAIS
>
> Sergio Dubner博士
>
> 科委会主席
>
> Edgardo Schapachnik博士
>
> 组委会主席
>
> 王玲洁译
>
>
>
> 2S. CLBBB. Dr. Ruiz Alais
>
> 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
>