Lesson Sixty Arrhythmogenicrightventricular dysplasia/cardiomyopathyand cardiac sarcoidosis distinguishing features when the diagnosis is unclear

●思考與分析

●心電學(xué)英語

Lesson Sixty Arrhythmogenicrightventricular dysplasia/cardiomyopathyand cardiac sarcoidosis distinguishing features when the diagnosis is unclear

Arrhythmogenic right ventricular dysplasia/cardiomyopathy（ARVD/C）is an inherited desmosomal cardiomyopathy characterized by fibrofatty replacement of the right ventricular（RV）myocardium.Disease expression is variable and the spectrum of structural changes range from subtle basal RV involvement to diffuse biventricular involvement.The broad spectrum of phenotypic manifestations makes the clinical diagnosis challenging.In the absence of histological evidence of myocardial fibrofatty replacement，the diagnosis is often established based on fulfilling various clinical criteria proposed by an International Task Force.Unfortunately，other infiltrative myocardial diseases，such as cardiac sarcoidosis（CS）1，may show overlap in clinical presentation and meet the 2010 Task Force Criteria as well. Being able to distinguish between the 2 is clinically important as the diagnostic and treatment strategies vary significantly and may involve genetic testing of family members or use of systemic immunosuppression.These reports suggest that there may be distinguishing features.

Patient Registry and Diagnostic Evaluation

Among 1140 patients enrolled，15 patients who were initially diagnosed with definite ARVD/C before referral were ultimately diagnosed as having CS.The control group consisted of probands who were selected based on（1）harboring a pathogenic ARVD/C-associated desmosomal mutation2，（2）fulfilling definite 2010 diagnostic criteria for ARVD/C，and（3）the availability of a comprehensive set of data for analysis.

The 2010 diagnostic criteria were used to establish a diagnosis of ARVD/C.Definite ARVD/C was characterized by the presence of≥2 major criteria，1 major and 2 minor criteria or 4 minor criteria.2

The diagnosis of CS was based on the Japanese guidelines revised in 2006 by the Japan Society of Sarcoidosis and Other Granulomatous Disorders.7

Patient Characteristics

Among 1140 patients enrolled in the Johns Hopkins ARVD/C registry，15 patients were subsequently diagnosed with CS.Forty-two probands harboring pathogenic ARVD/C-associated desmosomal mutations and fulfilling definite 2010 Diagnostic criteria for ARVD/C served as a control group（Table 1）.

Demographic Features and Clinical History

The predominant presenting symptom for both groups was palpitations and≈30%had syncope.The majority of patients in both groups presented initially with ventricular arrhythmias and among these patients，the morphology was predominantly left bundle branch block for both groups.Twenty-nine percent of patients with ARVD/C had a history of ventricular tachycardia（VT）storm，defined as≥3 episodes of VT within a 24-hour period at any point in the patient's history，as compared with 33%with CS（P=0.75）.Although therewas no statistical difference in ventricular premature beats between the 2 groups，there was a trend toward more ventricular premature beats in the group with ARVD/C（2375[971-7369]versus 596[400-785]；P=0.05）.

Patients with CS were older at the age of symptom onset（45[40-47]versus 23[18-29]years；P＜0.001）and more likely to have comorbidities including hypertension，coronary artery disease，and atrial arrhythmias. Heart failure symptoms were present only in patients with CS.Family history of disease（39.5%versus 0%；P=0.003）and premature sudden cardiac death（19% versus 0%；P=0.10）were present only in ARVD/C patients.

Electrocardiographic Characteristics

The electrocardiographic characteristics of the study population are shown in Table 2.

With respect to atrioventricular conduction，firstdegree atrioventricular block（Figure 1）was exclusively seen among patients with CS（53%versus 0%in ARVD/C；P＜0.001）.The median PR interval in patients with CS was 211（198-260）ms versus 159（140-177）ms for ARVD/C（P＜0.001）.Third degree atrioventricular block was also exclusively seen among subjects with CS as compared with ARVD/C patients（33%versus 0%；P≤0.001）.In this cohort，the sensitivity and specificity of having any atrioventricular block for the diagnosis of sarcoidosis were 66.7%and 100%，respectively.Interventricular conduction delay was observed more commonly in patients with CS as compared with those with ARVD/C.Nine of 15 patients with CS demonstrated a QRS duration＞120 ms including 5 with a right bundle branch block（RBBB）pattern and 4 with nonspecific interventricular conduction delay.Seven of 42 patients with ARVD/C demonstrated a QRS duration＞120 ms and all 7 had a RBBBpattern.The median QRS duration in patients with CS was significantly greater than in ARVD/C patients（132[100-142]ms versus 89[85-102]ms；P＜0.001）.

Electrophysiological Characteristics

During electrophysiology study，VT inducibility was observed in both groups（80%sarcoidosis versus 64%ARVD/C；P=0.34）.There were no significant differences in the mean cycle lengths or the morphology/axis of the induced VTs.The HV interval was significantly longer in patients with CS（50[50-55]ms versus 44[40-45]ms；P≤0.001）.The median number of VTs induced per patient was significantly greater among patients with CS（2.0[1-4]versus 1.0[1-2]；P=0.007）.

Imaging Characteristics

The RV ejection fraction was moderately reduced for both groups with no significant difference in the RV end-diastolic volume.The presence of major RV structural abnormality was present in 45%of ARVD/C patients and 33%of patients with CS（P=0.55）.Among 37 ARVD/C patients and 12 patients with CS who underwent cardiac MRI and had adequate image quality，49% of patients with ARVD/C had evidence of delayed enhancement，whereas 58%of patients with CS had delayed myocardial enhancement（P=0.74）.

Patients with CS had lower left ventricular（LV）ejection fractions（57[35-60]%versus 63[55-65]%；P＜0.001）.Furthermore，intramyocardial fat was significantly more common in ARVD/C patients（67% versus 8%；P＜0.001）.Septal involvement of gadolinium delayed enhancement（Figure 2）was more commonly associated with CS（42%versus 11%；P=0.004）. Mediastinal lymphadenopathy noted on standard chest roentgenogram，computed tomography，and MRI images was also seen more often in patients with CS（27% versus 0%；P=0.004）.

Among the 42 control patients，each patient had a pathogenic ARVD/C-associated desmosomal mutation and met diagnostic criteria for definite ARVD/C.The vast majority（76%）had a pathogenic mutation affecting the PKP2 gene.Application of the diagnostic criteria for CS to this group revealed that only 1 patient met criteria for CS.Among this group，15 patients（36%）underwent endomyocardial biopsies and 3 patients had fibrofatty infiltration meeting major tissue criteria based on the 1994 diagnostic criteria.

This study identified several important observations.First，ARVD/C patients present with symptoms at a younger age often are without cardiovascular comorbidities and more commonly have a family history of disease.Second，atrioventricular conduction abnormalities were seen exclusively in patients with CS.Third，LV dysfunction and heart failure symptoms were more commonly observed in patients with CS.Finally，MRI delayed enhancement of the septum was more commonlyassociated with CS along with extracardiac abnormalities such as mediastinal lymphadenopathy.

詞匯

sarcoidosis n.肉樣瘤病

immunosuppression n.免疫抑制

distinguish v.分別，區(qū)分，辨別出，看清

harbor n.&v.港口；藏匿

granulomatous adj.屬于肉芽腫的

Desmosomal adj.橋粒的

demographic adj.人口的

Comorbidity n.伴隨疾病，共患病

exclusively adv.專門，僅僅

gadolinium n.釓

mediastinal adj.中隔的

lymphadenopathy n.淋巴結(jié)病

roentgenogram n.倫琴射線照相

biopsy n.活組織切除

注釋

1.cardiac sarcoidosis是指“心臟結(jié)節(jié)病”，歸類于限制性心肌病，與心肌間質(zhì)炎癥有關(guān)，伴心室舒張功能異常，發(fā)病率不確定，多于老年發(fā)病，半數(shù)患者有心電圖異常表現(xiàn)，心性猝死是最常見的死亡原因，與完全性房室傳導(dǎo)阻滯或惡性快速心律失常有關(guān)。

2.desmosomal mutation指“橋粒突變”，橋粒（desmosome）是一種細(xì)胞間的連接結(jié)構(gòu)，促進(jìn)細(xì)胞與細(xì)胞的粘連、信號(hào)傳遞、各種組織發(fā)育和分化，已報(bào)道有10種不同的橋粒基因呈致病性常染色體顯性或隱性突變，引起的系列表型累及皮膚、毛發(fā)和心臟。

參考譯文

第60課致心律失常右心室發(fā)育不全/心肌病與心臟結(jié)節(jié)病——診斷不明時(shí)的鑒別特征

致心律失常右心室發(fā)育不全/心肌病（ARVD/C）是一種遺傳性橋粒（突變）心肌病，特征為纖維脂肪取代右心室心肌。疾病表現(xiàn)多變，結(jié)構(gòu)變化從右心室基底部輕微受累到雙心室彌漫性受累。廣泛的表型表現(xiàn)使得臨床診斷具有挑戰(zhàn)性。當(dāng)缺乏心肌纖維脂肪取代的組織學(xué)依據(jù)時(shí)，常基于滿足國際特別工作組建議的不同臨床標(biāo)準(zhǔn)而做出診斷。遺憾的是其他浸潤性心肌疾病，如心臟結(jié)節(jié)病（CS），可有重疊的臨床表現(xiàn)，并且也符合2010特別工作組標(biāo)準(zhǔn)。能夠區(qū)別這兩種疾病具有臨床意義，因?yàn)樵\斷和治療方案明顯不同，并涉及家庭成員的基因檢測或使用全身性的免疫抑制劑。……