Arrhythmogenic right ventricular cardiomyopathy/dysplasia: An update

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetic cardiomyopathy characterized by ventricular arrhythmias and structural abnormalities of the right ventricle (RV). The diagnosis is based on the International Task Force criteria. Cardiologists may not be aware of these diagnostic criteria for ARVC/D and may place too much importance on the results of MRI imaging of the right ventricle. Patients with ARVC/D usually have an abnormal 12-lead electrocardiogram, abnormal echocardiogram, and ventricular arrhythmias with a left bundle branch block morphology. If noninvasive testing suggests ARVC/D, invasive testing with an RV angiogram, RV biopsy, and electrophysiologic study is recommended. Once a diagnosis of ARVC/D is established, the main treatment decision involves whether to implant an implantable cardioverter-defibrillator. We also recommend treatment with β blockers. Patients with ARVC/D are encouraged to avoid competitive athletics. Recent advances in the understanding of the genetic basis of ARVC/D have revealed that ARVC/D is a disease of desmosomal dysfunction.     

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。     

Relative Utility of Magnetic Resonance Imaging and Right Ventricular Angiography to Diagnose Arrhythmogenic Right Ventricular Cardiomyopathy

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of the RV myocardium. Two imaging techniques used to assess patients suspected of having ARVC are magnetic resonance imaging (MRI) and right ventricular angiography (RVA). Traditionally, RVA has played a central role in the diagnosis of ARVC, but the non-invasive nature of MRI and its unique ability to detect fatty tissue infiltration has increased its popularity as a diagnostic tool. The objective of this study was to assess the relative diagnostic accuracy of MRI and RVA for ARVC. METHODS AND RESULTS: Seventeen patients (9 men, 8 women; ages 42 +/- 17 [range 16-78] years) with documented ventricular arrhythmias were investigated for ARVC. A positive diagnosis of ARVC was based on criteria set forth by the ISFC Working Group on Cardiomyopathies and Dysplasia. ECG-gated spin-echo and gradient-echo MR images in multiple planes and RAO/LAO RV angiograms were compared for diagnostic concordance. Based on working group criteria, 7 patients were diagnosed with ARVC. In ten patients, MRI suggested ARVC. The remaining 7 patients had no MRI findings suggestive of the disease. Four patients with MRI findings of ARVC were incorrectly diagnosed based on Task Force criteria. Conversely, 1 patient with a normal MRI met Task Force criteria for the diagnosis of ARVC. Based on RV angiograms, 7 patients had findings suggestive of ARVC. The 10 patients without AVRD (based on RVA) also did not meet the necessary criteria for diagnosis of ARVC using Task Force standards. RVA was 100% specific and 100% sensitive compared to MRI that was only 86% sensitive and 60% specific. MRI proved to be most reliable when the images demonstrated gross, lipomatous infiltration, evidenced by a large area of hyperintensity. When the results of MRI and RVA were congruent, the diagnosis was always accurate. CONCLUSION: RVA is more sensitive and specific to diagnose ARVC diagnosis than MRI, at least until MRI protocols are better developed. MRI results are most robust when indicators of ARVC are grossly apparent. False-positive diagnosis by MRI was primarily related to perceived motion abnormalities that were not seen by RVA. One of its greatest potential assets (fat detection) did not enhance diagnostic specificity.     

磁共振成像在致心律不齐性右室型心肌病的诊断价值

目的回顾性分析27例致心律不齐性右室型心肌病（ARVC）的磁共振成像（MRI）表现,探讨MRI在ARVC的诊断与预后判断中的价值。方法按照1994年WHO关于ARVC的诊断标准,2004年10月至2006年6月共27例临床诊断或病理确诊为ARVC（6例行心脏移植术）,男21例,女6例,平均年龄37．4（15～67）岁。采用1．5T超导MRI扫描仪对心脏形态（脂肪浸润、房室大小）、功能（室壁局部与整体运动功能）、心肌灌注与心肌存活等方面进行综合评价。结果形态学：88．89％（24／27）的病例MRI提示心肌脂肪浸润,62．96％（17／27）右室壁变薄,62．96％（17／27）右室心尖肌小梁明显粗乱,66．67％（18／27）右室流出道扩张,51．85％（14／27）右室心尖扩张,66．67％（18／27）右室下壁及游离壁扩张,40．74％（11／27）合并右房增大。心脏功能：18．52％（5／27）的病例右室局部运动功能异常,70．37％（19／27）整体运动功能异常,右室平均射血分数（EF）35％。40．74％（11／27）的患者合并左室扩大并室壁收缩运动明显减弱。心肌首过灌注示10．52％（2／19）的患者左室受累,36．84％（7／19）的患者左室和右室壁出现异常强化,提示心肌纤维或胶原变性。右室壁强化区域主要位于右室游离壁和右室流出道肌壁,左室则主要位于左室侧壁,少数合并左室心尖或室间隔,5例左室侧壁异常强化经术后病理证实为纤维组织。仅1例表现为右室流出道增宽,但左室心肌显著变薄,收缩运动明显减弱;有3例右室MRI无阳性表现,其中2例左室侧壁室壁变薄并运动异常,延迟显像为异常强化,另1例表现为类似扩张型心肌病样改变。结论MRI高度的软组织对比与多序列成像可对ARVC进行全面诊断与预后评价,但少数以左室异常表现为主而无明显或仅轻微右室异常的病例,MRI易误诊,其左室侧壁段的纤维化为ARVC相对特征表现。右室整体运动异常、广泛纤维脂肪浸润、合并左室扩张并运动异常为其预后不良的指标。     

Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia:Proposed Modification of the Task Force Criteria

The original 1994 International Task Force criteria for the clinical diagnosis of arrhythmogenic right yen tricular cardiomyopathy/dysplasia （ARVC / D） were based on structural, histological, ECG,     

The other side of arrhythmogenic right ventricular cardiomyopathy

Knowledge regarding arrhythmogenic right ventricular cardiomyopathy (ARVC) has increased dramatically since the publication of the original International Task Force diagnostic criteria in 1994. Based on symptomatic index cases and sudden cardiac death victims, the Task Force criteria emphasized manifestations observed only at the most severe end of the clinical spectrum of ARVC. It is now known that the phenotypic expression of the disease may vary considerably both in its severity and in the pattern of myocardial involvement. Recent familial studies have emphasized that, despite its name, the abnormalities of ARVC are not limited to the right ventricle. In recognition of the prevalence and clinical significance of left ventricular involvement in ARVC, a proposed modification to the original International Task Force criteria was recently published. We herein describe 3 cases of patients with ARVC who presented with left ventricular involvement as manifested by nonischemic pattern of delayed enhancement in the left ventricle.     

Clinical profile of arrhythmogenic right ventricular cardiomyopathy in Chinese patients.

OBJECTIVE: To study the clinical profile of Chinese patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). PATIENTS: Chinese patients who fulfilled the diagnostic criteria of ARVC proposed by the Task Force of the European Society of Cardiology and of the scientific council on cardiomyopathy of the International Society and Federation of Cardiology were recruited for analysis. METHODS: Clinical data of patients with ARVC including age, sex, family history, presenting symptoms, electrocardiograph (ECG), echocardiography, cardiac catheterization, magnetic resonance imaging (MRI), electrophysiology study (EPS) and therapeutic intervention were analyzed. RESULTS: Eleven patients (seven males) were diagnosed with ARVC. Mean age at clinical presentation was 42.6+/-14.8 years. Two patients (18.1%) had positive family history of ARVC or premature sudden cardiac death. The commonest presenting symptoms were palpitation (73%) and dizziness (46%). Spontaneous ventricular tachycardia (VT) was the presenting arrhythmia in 54% and 1 (9%) with ventricular fibrillation and cardiac arrest. Seven patients (64%) had the ECG abnormality as defined by the Task Force. Echocardiography showed right ventricular (RV) dilatation in five patients (46%) and all patients had normal left ventricular function. Nine patients (90%) had RV wall thinning or fibrofatty replacement on MRI examination. Inducible monomorphic VT was detected in four out of nine patients at EPS. All eight patients had normal coronary arteries and left ventriculogram but RV dilatation and global hypokinesia was seen in three patients. Implantable cardioverter defibrillators were implanted in five patients and two of them had shocks delivered during the follow-up period. CONCLUSION: In this study, familial incidence of premature sudden death in patients with ARVC appears to be low and left ventricular involvement in affected individuals is uncommon. MRI is still the best investigation for ARVC.     

Diagnostic value of endomyocardial biopsy guided by electroanatomic voltage mapping in arrhythmogenic right ventricular cardiomyopathy/dysplasia

Introduction: To improve the endomyocardial biopsy (EMB) diagnostic sensitivity for arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), we hypothesized a biopsy sampling focused on selected right ventricle (RV) low‐voltage areas identified by electroanatomic voltage mapping. Methods and Results: The study population (22 patients, 10 men; mean age 34 ± 10 years) included 11 patients with overt ARVC/D (group A) and 11 patients with suspected ARVC/D (group B), according to both arrhythmic profile and standardized noninvasive diagnostic criteria. In all 22 patients, an RV bipolar voltage mapping was performed with CARTO? system sampling multiple endocardial sites (262 ± 61), during sinus rhythm, with a 0.5–1.5 mV color range setting of voltage display. All 11 (100%) group A patients and 8 of the 11 (73%) group B patients (P = nonsignificant [NS]) presented RV low‐voltage areas (<0.5 mV). In 8 group A patients and in all 8 group B patients with a pathological RV voltage map, an EMB focused on the low‐voltage areas was performed. In 6 (75%) group A patients and in 7 (87%) group B patients (P = NS), voltage mapping‐guided EMB was diagnostic for ARVC/D. In the remaining 3 patients, only nonspecific histological findings were observed. Conclusions: The results of our study (1) confirm the high diagnostic sensitivity of RV voltage mapping in patients with overt ARVC/D, (2) document a high prevalence of RV low‐voltage areas even in patients with suspected ARVC/D, and (3) demonstrate that in patients with clinical evidence or suspicion for ARVC/D, presenting RV low‐voltage areas, EMB guided by voltage mapping may provide ARVC/D diagnosis confirmation.     

Arrhythmogenic right ventricular cardiomyopathy: From genetics to diagnostic and therapeutic challenges

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disease characterized by myocyte loss and fibro-fatty tissue replacement. Diagnosis of ARVC remains a clinical challenge mainly at its early stages and in patients with minimal echocardiographic right ventricular (RV) abnormalities. ARVC shares some common features with other cardiac diseases, such as RV outflow ventricular tachycardia, Brugada syndrome, and myocarditis, due to arrhythmic expressivity and biventricular involvement. The identification of ARVC can be often challenging, because of the heterogeneous clinical presentation, highly variable intra- and inter-family expressivity and incomplete penetrance. This genotype-phenotype “plasticity” is largely unexplained. A familial history of ARVC is present in 30% to 50% of cases, and the disease is considered a genetic cardiomyopathy, usually inherited in an autosomal dominant pattern with variable penetrance and expressivity; in addition, autosomal recessive forms have been reported (Naxos disease and Carvajal syndrome). Diagnosis of ARVC relays on a scoring system, with major or minor criteria on the Revised Task Force Criteria. Implantable cardioverter defibrillators (ICDs) are increasingly utilized in patients with ARVC who have survived sudden death (SD) (secondary prevention). However, there are few data available to help identifying ARVC patients in whom the prophylactic implantation of an ICD is truly warranted. Prevention of SD is the primary goal of management. Pharmacologic treatment of arrhythmias, catheter ablation of ventricular tachycardia, and ICD are the mainstay of treatment of ARVC.     

Noninvasive detection of myocardial fibrosis in arrhythmogenic right ventricular cardiomyopathy using delayed-enhancement magnetic resonance imaging

OBJECTIVES: We evaluated the role of myocardial delayed-enhancement (MDE) magnetic resonance imaging (MRI) for noninvasive detection of fibrosis in Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy is characterized by fibro-fatty replacement of the right ventricle (RV) leading to arrhythmias and RV failure. Endomyocardial biopsy can demonstrate fibro-fatty replacement of the RV myocardium; however, the test is invasive and carries a risk of perforation. METHODS: Thirty consecutive patients were prospectively evaluated for ARVD/C. Magnetic resonance imaging was performed on a 1.5-T scanner. Ten minutes after intravenous administration of 0.2 mmol/kg of gadodiamide, MDE-MRI was obtained. Diagnosis of ARVD/C was based upon the Task Force criteria and did not include MRI findings. RESULTS: Twelve (40%) of 30 patients met the Task Force criteria for ARVD/C. Eight (67%) of the 12 ARVD/C patients demonstrated increased signal on MDE-MRI in the RV compared with none (0%) of the 18 patients without ARVD/C (p <0.001). Endomyocardial biopsy was performed in 9 of the 12 ARVD/C patients. Of the nine patients, four had fibro-fatty changes consistent with the diagnosis of ARVD/C. Each of these patients had increased RV signal on MDE-MRI. None of the patients without ARVD/C had any abnormalities either on histopathology or on MDE-MRI. Electrophysiologic testing revealed inducible sustained ventricular tachycardia (VT) in six of the eight ARVD/C patients with delayed enhancement, compared with none of the ARVD/C patients without delayed enhancement (p=0.01). CONCLUSIONS: Noninvasive detection of RV myocardial fibro-fatty changes in ARVD/C is possible by MDE-MRI. Magnetic resonance imaging findings had an excellent correlation with histopathology and predicted inducible VT on programmed electrical stimulation, suggesting a possible role in evaluation and diagnosis of patients with suspected ARVD/C.     

Magnetic resonance imaging findings in patients meeting task force criteria for arrhythmogenic right ventricular dysplasia

INTRODUCTION: Magnet resonance imaging (MRI) findings in patients meeting Task Force criteria for the diagnosis of arrhythmogenic right ventricular dysplasia (ARVD) have not been systematically described. We report qualitative and quantitative MRI findings in ARVD using state-of-the-art MRI. METHODS AND RESULTS: MRI was performed on 12 patients with ARVD who were prospectively diagnosed using the Task Force criteria. The imaging protocol included breath-hold double inversion recovery spin-echo and gradient-echo images. Ventricular volumes and dimensions were compared to 10 age- and sex-matched normal volunteers. High intramyocardial T1 signal similar to fat signal was observed in 9 (75%) of the 12 patients and in none of the controls. Right ventricular (RV) hypertrophy was seen in 5 (42%) patients, trabecular disarray in 7 (59%), and wall thinning in 3 (25%). Both the RV end-diastolic diameter and the outflow tract area were significantly higher in ARVD patients compared to controls (51.2 vs 43.2 mm, P < 0.01; and 14.5 vs 9.3 cm2, P < 0.01, respectively). ARVD patients had a higher RV end-diastolic volume index and lower RV ejection fraction compared with controls (127.4 vs 87.5, P < 0.01; and 41.6% vs 57%, P < 0.01, respectively). CONCLUSION: High intramyocardial T1 signal indicative of fat is seen in a high percentage (75%) of patients who meet the Task Force criteria for ARVD. Trabecular disarray is seen more frequently than wall thinning and aneurysms. RV dimensions and volumes differ significantly in ARVD compared to controls, indicating a role for quantitative evaluation in the diagnosis of ARVD.     

Magnetic resonance imaging of arrhythmogenic right ventricular dysplasia: sensitivity, specificity, and observer variability of fat detection versus functional analysis of the right ventricle.

OBJECTIVES: The purpose of this study was to determine interobserver agreement for interpretation of magnetic resonance imaging (MRI) examinations of arrhythmogenic right ventricular dysplasia (ARVD) and to determine sensitivity and specificity of fat detection versus functional parameters measured by MRI. BACKGROUND: The interobserver variability of MRI and the relative importance of different MRI parameters (fat detection, regional and global right ventricular [RV] function) for ARVD diagnosis is unknown. METHODS: Two experienced observers blinded to the clinical history independently analyzed MRI datasets obtained from 40 patients evaluated for ARVD. Twenty normal subjects underwent MRI and served as control subjects. The MRI scans were performed according to a standard protocol on a 1.5-T scanner. The observers reported on fat infiltration, global and regional RV function, myocardial thinning, and chamber dilatation qualitatively. The RV volumes were measured on the cine sequences. RESULTS: Interobserver kappa scores for fat infiltration, global and regional RV function, wall thinning, and RV outflow dilatation were 0.74, 0.94, 0.89, 0.93, and 0.93, respectively. Correlation coefficients between observers for RV end-diastolic volume, end-systolic volume, and ejection fraction were 0.93, 0.94, and 0.95, respectively (p < 0.001). Fifteen patients were diagnosed with ARVD using Task Force criteria. Sensitivity of fat infiltration, RV enlargement, and regional RV dysfunction for diagnosing ARVD was 84%, 68%, and 78%, and specificity was 79%, 96%, and 94%, respectively. CONCLUSIONS: Qualitative assessment of RV structure and function is highly reproducible for experienced observers. Among the qualitative parameters, fat infiltration is less reproducible and lacks specificity compared with RV kinetic abnormalities.     

Epsilon Waves as an Extreme Form of Depolarization Delay: Focusing on the Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

Revision of the Task Force diagnostic criteria (TFC) for arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), in 2010, has increased the sensitivity for the diagnosis of early and familial forms of the disease. Epsilon wave (EW) is a major diagnostic criterion in the context of ARVC/D, however, it remains unquantifiable and therefore, may leave room for substantial subjective interpretation, thus, explaining the existing high inter-observer variability in the assessment of EW. EW, when present, coexists with other disease characteristics, which are sufficient for ARVC/D diagnosis, making EW generally not required for ARVC/D diagnosis. Nevertheless, EW remains an important part of the electrocardiographic phenotype of ARVC/D that may be useful in planning diagnostic work-up, which needs to be recognized.     

Arrhythmogenic right ventricular cardiomyopathy in two pairs of monozygotic twins

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inheritant disease with an autosomal dominant mode of transmission with incomplete penetrance and variable expression. Linkage analysis in affected families succeeds in identifying 9 loci determining 9 subtypes of the disease. Genotype phenotype correlation is unclear and the influence of various environmental factors is discussed. OBJECTIVES: Genotype phenotype correlation in 2 pairs of monozygotic twins with ARVC and the role of environmental factors are analyzed. PATIENTS AND METHODS: Among 40 pts with ARVC and their 195 relatives there were 2 pairs of monozygotic twins: brothers, age 47 y; and sisters, age 48 y. History, ECG, Holter monitoring, 2D and Doppler Echo, and MRI were analyzed. RESULTS: Twin brothers: ARVC was diagnosed in the proband after the episode of VT with LBBB morphology (enlarged right ventricle, focal hypokinesia of apex, MR evidence of adipose tissue in RV wall). Identical morphology of RV was seen in asymptomatic twin brother. The patient presenting arrhythmia has been rowing for 4 years. Twin sisters: diagnosis was done during family screening. Both were asymptomatic. RV morphology typical for ARVC was found discrete in one of them (bulges adipose tissue in the RV apex); the latter showed changes suggesting RV abnormality (mild segmental dilatation of infundibulum, adipose tissue in a free wall of the RV). No differences in previous viral infections and sports involvement were observed. CONCLUSIONS: 1. Clinical picture of ARVC in monozygotic twins is not identical. 2. Strenuous effort may be a factor triggering the arrhythmia in pts with ARVC.     

Syncope in the athlete – Minor changes,major diagnosis!

We report the case of a 17-year-old athlete who resorted to the emergency department for palpitations and dizziness while exercising. He mentioned two exercise-associated episodes of syncope in the last six months. He was tachycardic and hypotensive. The electrocardiogram showed regular wide complex tachycardia, left bundle branch block morphology with superior axis restored to sinus rhythm after electrical cardioversion. In sinus rhythm, it showed T-wave inversion in V1–V5. Transthoracic echocardiography revealed mild dilation and dysfunction of the right ventricle (RV) with global hypocontractility. Cardiac magnetic resonance (CMR) revealed a RV end diastolic volume indexed to body surface area of 180 ml/m², global hypokinesia and RV dyssynchrony, subepicardial late enhancement in the distal septum and in the middle segment of the inferoseptal wall. The patient underwent a genetic study which showed a mutation in the gene that encodes the desmocolin-2 protein (DSC-2), which is involved in the pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC). According to the modified Task Force Criteria for this diagnosis, the patient presented four major criteria for ARVC. Thus, a subcutaneous cardioverter was implanted, and the patient was followed up at the cardiology department.Arrhythmogenic right ventricular cardiomyopathy diagnosis is based on structural, functional, electrophysiological and genetic criteria reflecting underlying histological changes. This case depicts the essential characteristics for disease recognition.     

Evolving role of multidetector computed tomography in evaluation of arrhythmogenic right ventricular dysplasia/cardiomyopathy

The purpose of this study was to report 1 center's experience with multidetector computed tomography (MDCT) in the evaluation of patients suspected to have arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C). RV dilatation/dysfunction is 1 of the most important criteria for establishing the diagnosis of ARVD/C. Cardiac magnetic resonance imaging (MRI) is the most preferred imaging modality for the diagnosis of ARVD/C. However, many patients with suspected ARVD/C have implantable cardioverter-defibrillators, prohibiting the use of MRI. Thirty-one patients (19 men; mean age 41 +/- 12 years) referred for evaluation of known or suspected ARVD/C had a complete reevaluation including contrast-enhanced cardiac MDCT at the center. Two patients underwent both cardiac MRI and MDCT. Seventeen of 31 patients met Task Force criteria for ARVD/C and were confirmed to have ARVD/C. Multidetector computed tomographic images were analyzed for qualitative and quantitative characteristic findings of ARVD/C. Increased RV trabeculation (p <0.001), RV intramyocardial fat (p <0.001), and scalloping (p <0.001) were significantly associated with the final diagnosis of ARVD/C. RV volumes, RV inlet dimensions, and RV outflow tract surface area were increased in patients with ARVD/C compared with patients who did not meet the criteria. RV and left ventricular functional analysis was performed in 2 patients. In conclusion, cardiac MDCT has a strong potential to detect many qualitative and quantitative abnormalities of the right ventricle in patients with ARVD/C. Limitations include implantable cardioverter-defibrillators and motion artifacts, along with well-known radiation and contrast-induced reaction.     

Right ventricular scar‐related ventricular tachycardia in nonischemic cardiomyopathy: Electrophysiological characteristics,mapping, and ablation of underlying heart disease

1 Background

Right ventricular (RV)‐scar related ventricular tachycardia (VT) is often due to arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) or cardiac sarcoidosis (CS), but some patients whose clinical course has not been described do not fulfill diagnostic criteria for these diseases. We sought to characterize the electrophysiologic substrate and catheter ablation outcomes of such patients, termed RV cardiomyopathy of unknown source (RCUS).

2 Methods and results

Data of 100 consecutive patients who presented with RV cardiomyopathy and/or RV‐related VT for ablation were reviewed (51 ARVC/D, 22 CS; 27 RCUS). Compared to ARVC/D, RCUS patients were older (P = 0.001), less commonly had RV dilatation (P = 0.001) or dysfunction (P = 0.01) and fragmented QRS, parietal block, and T‐wave inversion. Compared to CS, R‐CUS patients had less severe LV dysfunction. Extent and distribution of endocardial/epicardial scar and inducible VTs in RCUS patients were comparable with ARVC/D and CS patients. At a median follow‐up of 23 months, RCUS patients had more favorable VT‐free survival (RCUS 71%, ARVC/D 60%, CS 41%, P = 0.03) and survival free of death or cardiac transplant (RCUS 92%, ARVC/D 92%, CS 62%, P = 0.01). No RCUS patients developed new criteria for ARVC/D or CS in follow‐up.

3 Conclusions

Up to one‐third of patients with RV scar‐related VT are not classifiable as ARVC/D or CS. These patients had a somewhat better prognosis than ARVC/D or sarcoid and did not develop evidence of these diseases during the initial 2 years of follow‐up. The extent to which this population comprises mild ARVC/D, CS, or other diseases is not clear.     

Patients with Scar-Related Right Ventricular Tachycardia: Determinants of Long-Term Outcome

Introduction: Patients with established arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) based on task force (TF) criteria and ventricular tachycardia (VT) are at risk of VT recurrence and sudden death. Data on patients with VT due to right ventricular (RV) scar not fulfilling TF criteria are lacking. The purpose of this study was to assess the long-term arrhythmia recurrence rate and outcome in patients with scar-related right VT with and without a diagnosis of ARVC/D.
Methods: Sixty-four patients (age 43.5 ± 15 years, 49 males) presenting with nonischemic scar-related VT of RV origin were studied. Scar was identified by electroanatomical mapping, contrast echocardiography, and/or magnetic resonance imaging (MRI). Patients were evaluated and treated according to a standard institute protocol.
Results: Twenty-nine (45%) patients were diagnosed with ARVC/D according to TF criteria (TF+) and 35 (55%) with RV scar of undetermined origin (TF–) at the end of follow-up (64 ± 42 months). Patients were treated with antiarrhythmic drugs, radiofrequency catheter ablation, and/or implantable cardioverter-defibrillator (ICD) implantation. VT recurrence-free survival for TF+ and TF– was 76% versus 74% at 1 year and 45% versus 50% at 4 years (P = ns). Patients with fast index VT (cycle length [CL]≤ 250 ms, n = 31) were more likely to experience a fast VT during follow-up than patients with a slow index VT (CL > 250 ms, n = 33) (61% vs 3%, P < 0.001).
Conclusions: Scar-related RV VTs have a high recurrence rate in TF+ and TF– patients. Patients presenting with a fast index VT are at high risk for fast VT recurrence and may benefit most from ICD therapy.     

Arrhythmogenic right ventricular cardiomyopathy due to a novel plakophilin 2 mutation: Wide spectrum of disease in mutation carriers within a family

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial disease, with male preponderance, characterized by progressive fibrofatty replacement of the right ventricle and ventricular arrhythmias. Mutations in plakophilin-2 (PKP2), a desmosomal protein, have been reported to underlie familial ARVC. We report a novel ARVC PKP2 mutation and present the clinical findings in three female mutation carriers. METHODS: We sequenced PKP2 from genomic DNA isolated from peripheral blood lymphocytes in a female proband who presented with cardiac arrest and in her four first-degree relatives. Clinical testing and diagnosis of ARVC was based on International Task Force criteria. RESULTS: The proband was diagnosed with ARVC due to right ventricular enlargement and regional hypokinesis, along with repolarization abnormalities and frequent ventricular ectopy. A novel 28 bp insertion in exon 11 of the PKP2 gene was found which causes a frameshift in the coding region. This results in a change in the amino acid sequence of the protein with a premature stop codon at position 740. Of the four relatives, only the mother and younger sister were identified as mutation carriers. The mother was phenotypically normal, while the younger sister has repolarization abnormalities and frequent ventricular ectopy. CONCLUSIONS: We report a novel PKP2 mutation that causes familial ARVC. All mutation carriers in this kindred group were women, and the family showed incomplete penetrance and variable expression of ARVC. Premature truncation of the plakophilin-2 protein appears to be the predominant mechanism whereby PKP2 mutations elicit the ARVC phenotype.     

Three-dimensional shape analysis of right ventricular remodeling in repaired tetralogy of Fallot

Understanding of right ventricular (RV) remodeling is needed to elucidate the mechanism of RV dysfunction in the overloaded right ventricle, but is hampered by the chamber's complex shape. We imaged 15 patients with repaired tetralogy of Fallot (TOF) and 8 normal subjects by magnetic resonance imaging in long- and short-axis views. We reconstructed the right ventricles in 3 dimensions using the piecewise smooth subdivision surface method. Shape was analyzed from cross-sectional contours generated by intersecting the right ventricle with 20 planes evenly spaced from apex to tricuspid annulus. Patients with TOF had dilated right ventricles compared with normal (end-diastolic volume index 216 +/- 99 vs 81 +/- 16 ml/m(2), p <0.001) but near-normal function (ejection fraction 40 +/- 9% vs 48 +/- 12%, respectively, p = NS). RV shape in patients with TOF differed from normal subjects in several ways. First, the right ventricle had a larger normalized cross-sectional area in patients with TOF (p <0.01 in apical planes). Second, the cross-sectional shape was rounder in patients with TOF (p <0.05 in apical planes). Also, the interventricular septum underwent relatively less enlargement so that it comprised only 27 +/- 4% of total RV surface area in patients with TOF, compared with 33 +/- 2% in normal subjects (p = 0.0001). In addition, the right ventricle in patients with TOF exhibited bulging basal to the tricuspid valve (4 +/- 4% of total RV length), unlike normals (1 +/- 2%, p <0.001). This basal bulging was amplified by tilting of the tricuspid annulus (29 +/- 11 degrees vs 15 +/- 7 degrees , respectively, p <0.005). In conclusion, the right ventricle remodels in several directions rather than following a shape continuum. Characterization of RV remodeling from 3-dimensional reconstructions provides novel insights.