[AF-FORUM] 59E 房颤和淀粉样变 Dr. Perez Riera

星期四四月 19 11:35:24 ART 2007

亲爱的L. Ayo，巴西圣保罗的Andrés Ricardo Pérez Riera回 
答您的问题

心脏淀粉样变，通常为原发的淀粉样变，或者是AL型 
淀粉样变，见于多发性骨髓瘤。是最典型的限制性心 
肌病一种。舒张功能受限而收缩功能正常（左室大小 
和功能一般正常）。其在美国和其他工业化国家很少 
见。其典型的表现就是舒张功能障碍。心室肌表现十 
分僵硬，心室充盈功能受损。他还常常继发于可以是 
全身疾病类型的其他疾病。这种限制性心肌病是不遗 
传的，但是有些可能会存在遗传倾向。它包括很多病 
因，特发性限制性心肌病，以及心肌纤维化疾病，嗜 
署红细胞心肌病，硬皮病，血色素沉积病，肉状瘤， 
以及其他一些良性肿瘤等等。

患心肌淀粉样变的患者通常有传导异常。患原发淀粉 
样变的患者预后不佳，合并收缩功能障碍者通常生存 
期小于6个月。即使经过积极治疗的患者，5年以上生 
存期者也很少见。

原发淀粉样变为非常见病,表现为不可溶解的纤维蛋 
白沉积在各个器官,如果心脏已经受累则预后不佳.针 
对其的治疗较难，因为为少见病，发生症状相对较 
晚，同时缺乏有效的治疗。接受治疗的患者平均生存 
期33.4个月。合并心衰的更差，平均生存期2.2和3.5个 
月（1）

继发淀粉样变，也称为AA型，很少累及心脏。但是， 
一种继发性淀粉样变的亚型，衰老型（senile  
amyloidosis ）通常累及到心脏和血管。这种亚型形成的 
蛋白沉积不同于AA型以及AL型。他的发生率随现在人 
类寿命的提高而越来越常见。这种心肌淀粉样变男性 
更多见，40岁以下患者很少见。

有研究显示，ECG表现为低电压，而室间隔厚度>198mm， 
诊断敏感率达72%，特异性91%。阳性预测值以及阴性预 
测值分别为79%和88%。该作者进而建议对怀疑淀粉样变 
患者，无创参数，ECG低电压以及超声显示室间隔增厚 
对诊断较有力（2）。

孤立性的心房淀粉样变（IAA）在老年淀粉样变中常 
见，主要影响心房传导，并继发房颤。 IAA的发生取 
决于年龄相关的淀粉巢的形成。而IAA进一步会受其他 
病理情况的影响，如瓣膜病，进而增加心房利钠肽 
（ANP）的合成与分泌。多元回归分析显示，淀粉样是 
房颤独立于年龄，性别以外的房颤独立于测因素，淀 
粉量与间质纤维化呈负相关（此点提示对该类患者 
ACEI治疗可能无益）（3）。风湿性心脏病患者合并房 
颤发生心房淀粉样变的几率较高。高血压，糖尿病， 
心肌肥厚，冠心病，心房扩张等为显示出与心房淀粉 
样变相关。淀粉沉积左心耳高于右心耳，同时与房颤 
时程以及女性性别相关。淀粉样变同时可能在长时期 
的房颤中参与结构重构，至少在瓣膜病房颤中是这样 
的。

这类病人的导管消融通常推荐用于室性心律失常对于 
淀粉样变患者房颤的消融治疗尚无文献报道. 通常的 
心肌淀粉样变治疗效果较差。由于舒张充盈异常，减 
少静脉及组织充盈压的药物如利尿剂可以应用，但又 
常常会减少心输出量。 ACEI 通常对这种限制性心肌病 
患者无效。地高辛、钙离子拮抗剂、倍他受体阻滞剂 
对于一些合并房颤患者的心室率控制有益。

对于室性心律失常可以射频消融最早激动点进行 
（4）。

对于淀粉样变所致的室间隔非对称性肥厚并梗阻者， 
间隔部（化学）是相对新兴的一个治疗（5）。

参考文献
1)       Chau EM,  Chow WH, Wang E, et al.Cardiac amyloidosis -
Experience in a tertiary cardiac referral centre. Int J Cardiol. 2007
Mar 22; [Epub ahead of print]

2)       Rahman JE, Helou EF, Gelzer-Bell R, Noninvasive diagnosis of
biopsy-proven cardiac amyloidosis. J Am Coll Cardiol. 2004; 43:410-415.

3)       Rocken C, Peters B, Juenemann G, et al.Atrial amyloidosis:
an arrhythmogenic substrate for persistent atrial fibrillation.
Circulation. 2002;106:2091-2097.

4)       Mlcochova H, Saliba WI, Burkhardt DJ,  et al.Catheter
ablation of ventricular fibrillation storm in patients with
infiltrative amyloidosis of the heart. J Cardiovasc Electrophysiol.
2006;17:426-430.

5)   Murphy RT,  Ratliff NB, Lever HM, et al.Use of percutaneous
transluminal septal myocardial ablation for relief of outflow tract
obstruction in cardiac amyloidosis: a novel therapeutic target.
Catheter Cardiovasc Interv. 2006; 68:637-641.

------------------------------------------------------------------------ 
------------
Dear Dr L. Ayo, from Florida USA. Here Andrés Ricardo Pérez Riera
from São Paulo Brazil answering.

Cardiac amyloidosis or "stiff heart syndrome," usually occurs during
primary amyloidosis, or AL type amyloidosis. It is usually seen in
multiple myeloma. Cardiac amyloidosisis the most typical type of
restrictive cardiomyopathy. Restrictive heart disease is
characterized by impairment of ventricular filling during diastole
with preserved systolic function (Normal or near normal LV size and
function).  It is least-common type in the United States and most
other industrial nations. Its principal abnormality is diastolic
dysfunction. The muscles of the ventricles become excessively rigid,
and the filling of the ventricles with blood between heartbeats is
impaired. It usually results from another disease, which occurs
elsewhere in the body. Restrictive cardiomyopathy does not appear to
be inherited, but some of the diseases that lead to the condition are
genetically transmitted. Idiopathic restrictive cardiomyopathy, and
others causes as endomiocardial fibrosis (apical obliteration of
right and left ventricular apices), Loeffler eosinophilic
endomyocardial disease and secondary restrictive cardiomyopathies:
hemochromatosis, amyloidosis, sarcoidosis, scleroderma, carcinoid
heart disease and glycogen storage disease of the heart.

Patients with cardiac amyloidosis have frequently conduction
disturbance. The natural history of primary amyloidosis is poor, and
for patients with symptomatic cardiac involvement, survival is
generally less than 6 months. Even among treated patients with
amyloid heart disease, survival beyond 5 years is rare.

Amyloidosis is an uncommon systemic disease characterized by
deposition of insoluble fibrillar protein in different organs and the
prognosis is poor if the heart is involved. Experience with
management of cardiac amyloidosis is difficult because of its rare
occurrence, late presentation and ineffective treatment. Patients who
received specific treatment for the underlying amyloidosis have an
average survival of 33.4 months. Patients with overt HF or with
untreated amyloidosis have a bad prognosis (mean survival of 2.2
months and 3.5 months, respectively)(1).

Secondary amyloidosis, also called AA type, rarely affects the heart.
However, a subtype of secondary amyloidosis called senile amyloidosis
involves the heart and blood vessels. Senile amyloidosis is caused by
overproduction of a protein different from both the AA and AL types.
Senile cardiac amyloidosis is becoming more common as the average age
of the population increases. Cardiac amyloidosis is more common in
men than in women. The disease is rare in people under age 40.

One model showed that if a low voltage on ECG was present and
interventricular septal thickness is >198mm, the diagnosis of cardiac
amyloidosis could be made with a sensitivity of 72% and a specificity
of 91%. In this model, the positive predictive and negative
predictive values were 79% and 88%, respectively. The authors
conclude that in patients with suspected cardiac amyloidosis, a
combination of noninvasive parameters-namely, a low voltage on ECG
and increased intraventricular septal thickness- on ECO is a useful
diagnostic tool(2).

Isolated atrial amyloidosis (IAA) one of the most common members of
the family of age-related ("senile") amyloids, affects atrial
conduction and seems to play a role in the pathogenesis of AF. The
occurrence of IAA depends on age leading to the formation of an
amyloid nidus. The progression and consequences of IAA are then
influenced by pathological conditions, such as valve diseases, that
increase synthesis and secretion of ANP. The presence of amyloid
correlated with age and P-wave duration and was related to sex, valve
diseases, and the presence of AF. The association between atrial
amyloid, AF, and P-wave duration is independent of age and sex.
According to multiple logistic regression analysis, amyloid is the
only age- and sex-independent predictor for the presence of AF.
Atrial fibrosis is not a predictor for AF, and the amount of amyloid
correlated inversely with the degree of interstitial fibrosis. The
inverse correlation between IAA and atrial fibrosis suggests that
these patients may not benefit from treatment with ACE inhibitors to
reduce the amount of atrial fibrosis(3). Patients with chronic AF and
rheumatic heart disease have a very high prevalence of atrial
amyloidosis. Hypertension, diabetes mellitus, hypertrophy of the
heart, coronary atherosclerosis, and dilatation of the atria show no
significant relationship to the incidence or severity of atrial
amyloidosis. Amyloid deposition is more frequent in left than in
right atrial appendage and correlates with AF duration and female
gender. Amyloid deposition could constitute an additional
histological feature in the structural remodeling of atria during
long-standing AF, at least in rheumatic valve disease. Persistence of
AF might play a pivotal role in promoting amyloid deposition. Amyloid
deposition as a cause of atrial remodelling in persistent valvular
atrial fibrillation.  Radiofrequency catheter ablation (RFCA) is
refereed only for ventricular arrhythmias. There are not reference of
RFCA treatment for AF secondary to amyloidosis.Treatment of cardiac
amyloidosis, in general, difficult and often ineffective. Because of
the abnormalities of diastolic filling that are characteristic of
this condition, general measures to reduce venous and systemic
congestion such as with the use of diuretics, are desirable but often
result in an attendant reduction in stroke volume and cardiac output.
ACEI are generally ineffective in presence of restrictive
cardiomyopathy. Digoxin, calcium channel blocking drugs, and beta-
adrenergic blocking agents may be used with benefit to control the HR
response in the subgroup of patients with AF.

For ventricular arrhythmias RFCA is applied in the sites of earliest
activationlocalized within the LV(4).

The use of use of percutaneous transluminal septal myocardial
ablation is  a novel therapeutic target for relief of LVOT in
refractory severe HF who had asymmetric septal hypertrophy
obstructive cardiac amyloidosis (5).

Rerefences
1)       Chau EM,  Chow WH, Wang E, et al.Cardiac amyloidosis -
Experience in a tertiary cardiac referral centre. Int J Cardiol. 2007
Mar 22; [Epub ahead of print]

2)       Rahman JE, Helou EF, Gelzer-Bell R, Noninvasive diagnosis of
biopsy-proven cardiac amyloidosis. J Am Coll Cardiol. 2004; 43:410-415.

3)       Rocken C, Peters B, Juenemann G, et al.Atrial amyloidosis:
an arrhythmogenic substrate for persistent atrial fibrillation.
Circulation. 2002;106:2091-2097.

4)       Mlcochova H, Saliba WI, Burkhardt DJ,  et al.Catheter
ablation of ventricular fibrillation storm in patients with
infiltrative amyloidosis of the heart. J Cardiovasc Electrophysiol.
2006;17:426-430.

5)   Murphy RT,  Ratliff NB, Lever HM, et al.Use of percutaneous
transluminal septal myocardial ablation for relief of outflow tract
obstruction in cardiac amyloidosis: a novel therapeutic target.
Catheter Cardiovasc Interv. 2006; 68:637-641.

All the best for all
Andrés Ricardo Pérez Riera MD
Chief of Electro-Vectocardiology Sector of the Discipline of Cardiology,
ABC Faculty of Medicine (FMABC), Foundation of ABC (FUABC) - Santo
André São Paulo - Brazil.
riera在uol.com.br

--
Dr. Sergio Dubner
President of Scientific Committee

Dr. Edgardo Schapachnik
President of Steering Committee