致心律失常性右心室心肌病

致心律失常性右心室心肌病是一种少见的心肌疾病 ,易发生心律失常、心力衰竭和猝死。本文将对其发病机制、临床表现、病理特征、诊断及治疗方面的研究进展进行综述     

Arrhythmogenic right ventricular dysplasia/cardiomyopathy. A review and update

The arrhythmogenic right ventricular dysplasia/cardiomyopathy is an important cause of sudden arrhythmic death, often exertional, in young individuals and athletes. Although the aetiology remains partially unknown, genetic abnormalities have been demonstrated. Reported prevalence is 1 in 5000 individuals but it is considered there are many non-diagnosed cases.

The characteristic pathologic finding is the progressive fibro-fatty replacement of the right ventricular myocardium. The clinical manifestations vary from asymptomatic patients with an episode of sudden cardiac death as first symptom to chronically symptomatic patients with recurrent palpitations and/or right or biventricular failure.

Approximately a third of the patients show the characteristic Epsilon wave in the 12-lead ECG which is a useful screening test. Signal-averaged ECG frequently demonstrates late potentials. The two-dimensional echocardiography, magnetic resonance imaging, computerized tomography and right ventricular cineangiography show morphologic abnormalities in the right ventricle.

Therapy is directed to prevent and/or treat malignant ventricular tachyarrhythmias with medications, implantable cardioverter defibrillator and radiofrequency ablation in selected cases.     

致心律失常性右心室心肌病患者心室晚电位与室性心动过速关系

目的探讨致心律失常性右心室心肌病(arrhythmogenic right ventricular dysplasia/cardiomyopathy,ARVD/C)合并室性心动过速与心室晚电位的关系。方法ARVD/C38例,男28例,女10例,年龄(35±15)岁。心电图检查进行信号叠加,记录心室晚电位量化参数:总QRS时限(total QRS duration,QRST)、QRS终末部位电压低于40μV时限(low potential terminal signals,LPS40)、QRS最后40ms电压方根均数(root mean square of the last 40 ms,RMS40);动态心电图检查记录室性心动过速和室性期前收缩。使用χ2及Mann-Whitney秩和检验统计。结果①心室晚电位阳性25例,其中室性心动过速18例;心室晚电位阴性13例,室性心动过速3例(P=0.004);②室性心动过速阳性21例,阴性17例,QRST:室性心动过速阳性组109～233(中位数147)ms,阴性组85～158(中位数104)ms(P=0.000);LPS40:阳性组15～158(中位数53)ms和阴性...     

Clinico-radiological profile of arrhythmogenic right ventricular dysplasia at a tertiary care center: Two year experience

BackgroundArrythmogenic right ventricular dysplasia (ARVD/C) refers to fibro fatty infiltration replacement of ventricular myocardium especially that of right ventricle. The clinical presentation varies from asymptomatic state to ventricular tachycardia, heart failure and even sudden death. Diagnosis is established using modified ARVD/C taskforce criteria. Among all the various modalities of diagnosis, magnetic resonance imaging (MRI) gives most comprehensive evaluation of both morphological and functional abnormalities in this disease. MRI may not only obviate need for myocardial biopsy but also give insights into the nature of disease like presence of left ventricular myocardial involvement. We present our 2 years experience of ARVD/C patents who were admitted in our center and in whom diagnosis of ARVD/C was supported by excellent MR imaging.Materials and methodsThis study was conducted by Department of Radiology and Cardiology SKIMS, a tertiary care center for a period of 2 years. Patients with suspected ARVD/C based on clinical, electrophysiological and echocardiographic findings were subjected to MR imaging. Patients were excluded if they had history metallic implants, claustrophobia or were uncooperative. In this study stress was laid on diagnostic role of MRI in ARVD/C.ResultsThe median age at presentation was 31 years (range 21–43 years). 80% of patients were males. Most common clinical presentation was palpatations (40%). Syncope was present in 27% and heart failure in 13%. EKG suggestive of ARVD was seen in 87%. Echocardiographic features suggestive of ARVD/C was seen in all 15 patients. Family history of premature sudden death less than 35 years old was present in one patient only. MRI evidence classical for ARVD/C was seen in 80%.ConclusionDemographic features and mode of presentation of our patients is consistent with what has been rest of the world. We performed MRI in all patients to increase the specificity of our diagnosis. MR imaging allows a three-dimensional evaluation of the right ventricle and provides the most important anatomic, functional, and morphologic criteria for diagnosis of ARVD/C within one single study. MR imaging appears to be the optimal imaging technique for detection and follow-up of clinically suspected ARVD/C.     

Clinical profile of four families with arrhythmogenic right ventricular cardiomyopathy caused by dominant desmoplakin mutations.

AIMS: To characterize the clinical profile of patients belonging to families affected with autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) due to mutations of the gene encoding for the cell-to-cell adhesion protein desmoplakin (DSP). METHODS AND RESULTS: Thirty-eight subjects belonging to four families showing different DSP mutations (three missense and one in the intron-exon splicing region) underwent clinical and genetic investigation, including annual 12-lead ECG, signal averaged ECG, 24 h Holter ECG, and two-dimensional echocardiography. Twenty-six family members (11 males and 15 females) were found to carry a DSP mutation. After a follow-up of 1-24 years, median 6, 14 (54%) fulfilled (mean age at diagnosis 33+/-15 years) and 12 (mean age 43+/-24 years at the last follow-up) did not fulfil the established diagnostic criteria of ARVC, although five of them had some cardiac abnormalities. Clinical presentations were palpitations in six, sudden death (SD) in three, syncope in one, and chest pain with increased myocardial enzymes in two. Abnormal 12-lead ECG findings were present in 15 cases (58%), ventricular arrhythmias in 12 (46%), and late potentials in 11 (42%). Fourteen (54%) had abnormal echocardiographic findings, with left ventricular involvement in seven of them. SD occurred in six subjects and in three it was the first symptom of the disease; moreover, one subject died due to heart failure. The annual disease-related death and SD/aborted SD were 0.028 and 0.023 patient/year, respectively. CONCLUSION: Familial ARVC caused by DSP mutations is characterized by a high occurrence of SD even as first clinical manifestation. Left ventricular involvement is not a rare feature of the disease, which frequently escapes clinical diagnosis by applying the currently available criteria. Genetic screening is mandatory for early identification of asymptomatic carriers and preventive strategies within a family with a genotyped index case.     

致心律失常性右室心肌病（ARVC）临床和病理观察（附3例报告）

目的 通过所遇的病例,学习有关献,提高对ARVC的认识,特别是对中青年的不明原因心律失常,早期识别、预防猝死。讨论 病因,目前普遍认为是常染色体遗传病,可为显性、不完全外显及隐性。也提出心肌被脂肪组织所替代是慢性心肌炎引起的后天性损伤（炎症、坏死）和修复过程演进的结果。诊断 主要依据心慌、头晕、昏厥等症状,结合心电图有典型的室性早搏、短车室速、室颤,QRS时限≥110ms,进一步可对其心脏形态及功能进行评价。组织学检查为诊断ARVC的金标准,但心内膜活检须注意取材部位,预防室壁穿孔等并发症。治疗 目前主张一般情况用药物抗心律失常,严重可植入除颤器,也可经外科手术治疗或心脏移植。     

Exercise testing for long-term follow-up in arrhythmogenic right ventricular cardiomyopathy

Objectives

We investigated arrhythmia, electrocardiography and physical work capacity (PWC) in the follow-up of ARVC.

致心律失常性右心室心肌病一家系报告

目的 探讨家族性致心律失常性右心室心肌病的心电图特点。方法报道致心律失常性右心室心肌病患者一家系并结合文献分析其特点。结果本家系中右心室心肌病的发病率很高,男女患病比例相仿,疾病的表现度有较大的可变性,有时可无症状。先证者心电图发现Epsilon波且以V3R最为明显,所有患者V1～V3QRS波群终末部均有挫折,QRS时间均〉110ms,V3～V4均有T波倒置现象。结论致心律失常性右心室心肌病存在明显的遗传倾向,临床上以室性心律失常及猝死为主要表现,心电图具有相对特征性改变。     

Endomyocardial biopsy in right ventricular cardiomyopathy

Right ventricular cardiomyopathy is characterized by a progressive myocyte loss and fibro-fatty substitution of the right ventricle. The aim of our study was to assess the diagnostic accuracy of right ventricular endomyocardial biopsy. Using an imaging analyser system, histomorphometric parameters of myocytes, interstitium, fibrous tissue and fatty tissue were evaluated on endomyocardial biopsy from 30 patients with arrhythmogenic right ventricular cardiomyopathy, 29 patients with dilated cardiomyopathy and 30 control patients. The percent area of myocytes decreased from 78.10 ± 7.34 in control to 63.39 ± 9.22 in dilated cardiomyopathy (P < 0.05) and to 47.28 ± 15.01 in arrhythmogenic right ventricular cardiomyopathy (P < 0.01). Fibrous tissue increased from 8.10 ± 3.89 in control to 21.80 ± 9.29 in dilated cardiomyopathy (P < 0.05) and to 24.60 ± 11.37 in arrhythmogenic right ventricular cardiomyopathy (P < 0.05). Fatty tissue varied from 0.33 ± 1.44 in control and 0.07 ± 0.31 in dilated cardiomyopathy to 13.30 ± 17.30 in arrhythmogenic right ventricular cardiomyopathy (P < 0.05). Fatty tissue was a feature of arrhythmogenic right ventricular cardiomyopathy (67% of patients vs. 6% of control and dilated cardiomyopathy patients). Diagnostic values typifying arrhythmogenic right ventricular cardiomyopathy, obtained by excluding any overlapping between confidence intervals in the three groups, were: myocytes <44.95%; fibrous tissue >40.38%, and fatty tissue >3.21%, with 67% sensitivity and 91.53% specificity for at least one parameter. In conclusion, a significant difference between arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy and control exists in terms of amount of myocytes, fibrous tissue and fatty tissue. Presence of fatty tissue and fibrous tissue exceeding 3.21% and 40.38%, respectively should be considered highly suspect for arrhythmogenic right ventricular cardiomyopathy in right ventricular endomyocardial biopsy.     

26例致心律失常右室心肌病的临床和心电图特点分析

目的:探讨致心律失常右室心肌病(ARVC)的临床和心电图特点。方法:收集、查阅1993～2003年 上海市中山医院心内科26例诊断为ARVC的入院病例资料,分析其窦性心律和(或)室性心动过速发作时的常 规体表心电图各项参数,并作统计分析。结果:26例ARVC病例中,入院年龄为13～70(37.7±15.1)岁,首发症 状年龄为8～55(33.2±13.9)岁;13例(50%)有晕厥发作史。25例常规心电图检查中有11例(44.0%)发现Ep silon波,多见于右侧胸导联(V1～3),部分病例可出现于Ⅱ、Ⅲ和aVF导联,其中1例在大多数导联上均可见Epsi lon波;8例(33.3%)右侧胸导联可见T波倒置。右侧胸导联的平均QRS间期(QRS1=V1+V2+V3间期的平 均值)为0.1～0.22(0.13±0.030)s,左侧胸导联的平均QRS时间(QRS2=V4+V5+V6间期的平均值)为0.08 ～0.18(0.11±0.02)s(P<0.01),QRS1/QRS2为1.2±0.2(1.0～1.9),其中16例(61.5%)两者之比≥1.2。4 例出现肢体导联低电压,3例出现完全性右束支传导阻滞,类右束支、左前分支、左后分支和室内传导阻滞各1 例,1例在aVF导联出现显著的T波电交替。结论:心电图中Epsilon波和右胸导联QRS间期延长,有助于诊断 ARVC。     

Long-term follow-up of the signal-averaged ECG in arrhythmogenic right ventricular cardiomyopathy: correlation with arrhythmic events and echocardiographic findings.

AIMS: The aims of our study were to evaluate late potential changes during long-term follow-up in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and to correlate these results with echocardiographic findings and sustained ventricular tachycardia (VT) occurrence. METHODS AND RESULTS: We studied 31 patients (22 males and 9 females; mean age 29+/-16) during 8 years of follow-up by signal-averaged ECG (SAECG) and echocardiography. Ten subjects experienced episodes of sustained VT. During follow-up, all the SAECG parameters showed a progressive significant increase in late potentials. In contrast, echocardiographic indices did not show evidence of relevant modifications. Patients with sustained VT were characterized by significantly lower left and right ventricular ejection fractions, longer values of filtered QRS at 25/40/80-250 Hz filters, and longer high-frequency low-amplitude (HFLA) signals at 25-250 Hz at baseline. The analysis of SAECG modification during follow-up indicated that only HFLA signals at 25-250 Hz increased significantly in the sustained VT group. CONCLUSION: We detected a progressive increase in delayed ventricular conduction by SAECG not associated with significant echocardiographic changes. Therefore, the conduction disturbance seems to increase independently from anatomical alterations. The baseline SAECG and echocardiographic parameters, more than their modifications during follow-up, appear to be useful in identifying patients with sustained VT.     

致心律失常性右心室心肌病植入心律转复除颤器治疗一例

患者女性,30岁,以"心悸6年,加重伴间断晕厥半月"入院.近6年活动后心悸,近2年双下肢和颜面间断水肿,半月来症状加重,并出现晕厥,在当地医院血压未测出,心电图证实为持续性室性心动过速(室速),静脉推注胺碘酮150 mg后转为窦性心律,意识恢复,转入我院.     

Predictors of appropriate implantable defibrillator therapies in patients with arrhythmogenic right ventricular dysplasia

BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited cardiomyopathy characterized by ventricular arrhythmias and sudden cardiac death. The risk factors for sudden death and indications for implantable cardioverter-defibrillator (ICD) placement in patients with ARVD are not well defined. OBJECTIVES: The purpose of this study was to determine which clinical and electrophysiologic variables best predict appropriate ICD therapies in patients with ARVD. Particular attention focused on whether the ICD was implanted for primary or second prevention. METHODS: We enrolled 67 patients (mean age 36 +/- 14 years) with definite or probable ARVD who had undergone ICD placement. Appropriate ICD therapies were recorded, and Kaplan-Meier analysis was used to compare the event-free survival time between patients based upon the indication for ICD placement (primary vs secondary prevention), results of electrophysiologic testing, and whether the patient had probable or definite ARVD. RESULTS: Over a mean follow-up of 4.4 +/- 2.9 years, 40 (73%) of 55 patients who met task force criteria for ARVD and 4 (33%) of 12 patients with probable ARVD had appropriate ICD therapies for ventricular tachycardia/ventricular fibrillation (VT/VF; P = .027). Mean time to ICD therapy was 1.1 +/- 1.4 years. Eleven of 28 patients who received an ICD for primary prevention (39%) and 33 of 35 patients who received an ICD for secondary prevention (85%) experienced appropriate ICD therapies (P = .001). Electrophysiologic testing did not predict appropriate ICD interventions in patients who received an ICD for primary prevention. Fourteen patients (21%) received ICD therapy for life-threatening (VT/VF >240 bpm) arrhythmias. There was no difference in the incidence of life-threatening arrhythmias in the primary and secondary prevention groups (P = .29). CONCLUSION: Patients who meet task force criteria for ARVD are at high risk for sudden cardiac death and should undergo ICD placement for primary and secondary prevention, regardless of electrophysiologic testing results. Further research is needed to confirm that a low-risk subset of patients who may not require ICD placement can be identified.     

新型磁共振对典型及早期致心律失常性右室心肌病诊断价值的探讨

目的 用有黑血技术的新型磁共振（MRI）对典型致心律失常性右室心肌病（ARVC）进行检查，以确定新型MRI诊断ARVC的特异性和敏感性，并通过对确诊的ARVC患的一级亲属行MRI检查，以探讨MRI对早期ARVC的诊断价值。方法 10例ARVC患（除1例猝死首诊外）及其7个家系的54名成员全部接受询问病史，体检，心电图，心脏超声等检查；10例临床患均接受MRI检查，分析和确定其影响特征及诊断条件，在此基础上对部分家系成员行MRI检查以发现早期ARVC患。结果 临床患有阵发性室性心动过速（8／8），晕厥（9／10），心力衰竭（3／10）和猝死（3／10）。心电图均有左束支传导阻滞型阵发性室性心动过速，心室晚电位（VLP）均阳性（8／8）。MRI检查显示临床患均有明显右心室（RV）扩大及室壁广泛强信号，经压脂处理后心肌信号呈岛状或连续中断，为特征性纤维脂肪替代影像，患均有RV运动减低或室壁瘤形成，部分伴左心室受累（3／8）。家系筛选发现8例异常，拟诊为早期ARVC，2例有心电图异常，2例VLP阳性。MRI显示，8例心室壁均有局限性纤维脂肪病的影像改变，4例有RV扩大，2例可疑扩大，6例RV心尖部血流淤滞现象。结论 带黑血技术的新型MRI是目前诊断ARVC和早期ARVC的最具特异性和敏感性的检查手段。     

Catastrophic global heart failure in a patient with non-arrhythmogenic right ventricular dysplasia

Summary A young patient with congestive heart failure had pathological findings of myocarditis super-imposed on the substrate of a non-arrhythmogenic form of right ventricular dysplasia. The only clinical findings suggestive of right ventricular dysplasia were T-wave inversions on the right precordial leads.     

Genetics of arrhythmogenic right ventricular cardiomyopathy

Recent advances in molecular genetics of arrhythmogenic right ventricular cardiomyopathy (ARVD) are reviewed. In particular, the finding of mutations in the gene coding for cardiac ryanodine receptor (hRYR2), both in patients affected with ARVD2 and in patients affected with catecholaminergic ventricular arrhythmias or with familial ventricular tachyarrhythmia, is discussed. Novel data support the hypothesis that apoptosis may be a key step in molecular pathogenesis of ARVDs. A series of studies on drugs with apparent protective effect against apoptosis in myocardial cells might open new perspectives in the therapeutic approach.