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Unlabelled: We searched for special features in patients with complete and incomplete right bundle branch block diagnosed as having arrhythmogenic right ventricular cardiomyopathy/dysplasia. Whether right bundle branch block is a frequent finding in arrhythmogenic right ventricular cardiomyopathy should be studied. The question is whether special features exist such as T-wave inversions, localized right precordial QRS prolongation and r'/s ratio<1., Results: ARVC could be diagnosed according to ISFC/ESC criteria in 374 patients. CRBBB was found in 22 cases (6%) and iCRBBB was present in 47 cases (12.5%). In CRBBB T wave inversions ≥ V4 was found in 10 cases (n.s.) and r'/s ratio<1 was present in 12 cases (p<0.001). In iCRBBB T wave inversions ≥ V4 was found in 10 cases (n.s.) and ST segment elevation in right precordial leads was present in 19 cases (p<0.005). In all patients with ARVC localized right precordial QRS prolongation was found. Patients with CRBBB have a bad prognosis: 17 of 22 patients developed biventricular heart failure requiring heart transplantation and diuretic therapy., Conclusions: CRBBB and iCRBBB are infrequent findings in arrhythmogenic right ventricular cardiomyopathy. Complete right bundle branch block is characterized by r'/s ratio<1. There are no significant T wave inversions ≥ V4. Incomplete right bundle branch block is characterized by ST segment elevation in right precordial leads but not by T wave inversions ≥ V4., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Context: QRS fragmentation, including epsilon potentials, terminal activation delay and prolonged S wave upstroke, has been recently described as a diagnostic criterion of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). Whether QRS fragmentation is a marker of recurrent ventricular tachycardia, primary ventricular fibrillation, implantable cardioverter defibrillator (ICD) discharge and sudden cardiac death in these patients is unknown., Results: Three hundred and thirty-five patients (167 men, mean age 46.3 ± 14.6 years) with ARVC/D according to International Society and Federation of Cardiology/European Society of Cardiology (ISFC/ESC) criteria were analyzed retrospectively. Patients with complete and incomplete right bundle branch block were excluded from the analysis. At 6.3 ± 3.1 years mean follow-up, seven patients (0.02%) had died suddenly, 39 patients (0.13%) experienced recurrent ventricular tachycardia, 32 patients (0.1%) presented with primary ventricular fibrillation and 30 patients (0.1%) had recurrent ICD discharges. QRS fragmentation was significantly associated with arrhythmic events (P < 0.0000001 for the endpoint of sudden cardiac death, P < 0.01 for recurrent ventricular tachycardia, P < 0.0001 for primary ventricular fibrillation and P < 0.001 for recurrent ICD discharges, respectively)., Conclusion: QRS fragmentation predicts arrhythmic events in patients with ARVC/D. Further, properly designed prospective studies are warranted to confirm these findings.

The case of a 26-year-old male with sudden cardiac arrest due to ventricular fibrillation and the final diagnosis of arrhythmogenic right ventricular dysplasia-cardiomyopathy (ARVD/C) and initial early repolarization phenomenon is presented in detail. An additional analysis of early repolarization in additional 359 patients with ISFC/ESC diagnostic criteria of ARVD/C revealed a frequency within the threshold in healthy volunteers with 3% in isolated lateral leads and 7% in inferolateral leads. The high frequency of electrocardiographic early repolarization limited to inferior leads (22%) is probably due to late depolarization and represents an already reported typical feature of ARVD/C.

Background: Epsilon potentials in right precordial leads are reliable diagnostic electrocardiographic (ECG) criteria of arrhythmogenic right ventricular dysplasia-cardiomyopathy (ARVD/C). Sensitivity of epsilon potentials can be enhanced by highly amplified and modified ECG recording technique. Nevertheless, in many cases the definition of epsilon potentials remains difficult., Objective: To overcome these limitations, the value of QRS fragmentation in a standard 12-lead ECG was analyzed in 360 patients with ARVD/C (176 men, mean age 47.3 +/- 13.7 years)., Methods: Analysis of QRS fragmentation of the whole collective of patients was compared with the detection of epsilon potentials in highly amplified right precordial and modified limb leads in a subgroup of 207 patients. Fifty-two phenotypically and genotypically nonaffected subjects from systematic family screening in 10 families with known plakophilin-2 and desmoplakin mutations served as a control group., Results: QRS fragmentation could be found in a total of 306 of 360 patients (85%); 2.09 +/- 1.8 fragmented QRS complexes (range 1 to 7) could be found per patient. Fragmented QRS complexes in only 1 right precordial lead were found in 106 cases. In 190 cases, QRS fragmentation was present in more than 1 lead, including all 12 standard leads. Epsilon potentials in highly amplified right precordial and modified limb leads could be found in a total of 159 cases (77%). Typical epsilon potentials in highly amplified right precordial leads could be found in 97 cases (47%)., Conclusion: QRS fragmentation in ARVD/C has a high diagnostic value similar to epsilon potentials by a highly amplified and modified recording technique.

Aims: Provocable coved-type ST-segment elevation in right precordial leads is an observation in approximately 16% of patients with typical arrhythmogenic right ventricular cardiomyopathy (ARVC). The value of this observation should be analysed in a long-term follow-up of 17 patients identified by systematic ajmaline challenge., Methods and Results: At first evaluation, one female had an aborted sudden cardiac death and eight patients suffered from recurrent syncopes. Intrathoracic cardioverter defibrillator (ICD) implantation was done in the patient with aborted sudden cardiac death and in six patients with recurrent syncopes. One of these six patients had intermittant 2-3 degrees AV block. Another patient had inducible ventricular tachycardia (VT) at electrophysiological study. Follow-up over more than 3 years in all but one patient was characterized by documented monomorphic VT in the patient with inducible VT and ICD implantation (6%). The patient with aborted sudden cardiac death had only non-sustained VT's shortly after ICD implantation. From the eight patients without syncopes two more patients developed AV block and SA block 3 degrees (18%). Lead-associated complications appeared in three of eight patients with ICDs (38%). Repeated ajmaline challenge was positive in four of eight cases (50%). One patient had a new mutation encoding for SCN5A gene., Conclusion: Ajmaline challenge in typical ARVC characterizes a subgroup of elderly, predominantly female patients with the risk of developing conduction disease. Tachycardia-related events are rare. The indication of ICD implantation in recurrent syncopes is critical as the rate of lead-associated complications in a more than 3 years follow-up is high.

Objectives: Limited data are available on the course of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) because of the low frequency of this diagnosis. A long-term follow-up was analysed in typical ARVD/C patients from different primary and tertiary centres, and risk factors for sudden cardiac death (SCD) and end-stage heart failure were assessed., Methods and Results: A total of 313 patients (197 males) with a mean age of 44.8 +/- 16.5 years were included, with symptoms including aborted SCD (7%), ventricular arrhythmias (47%), additional chest pain (42%), syncopes (17%), and atrial arrhythmias (12%); follow-up duration was 8.5 years. The total annual mortality rate was 0.3%, from SCD in 0.2% and heart failure in 0.1%. In symptomatic or high-risk patients, the annual rate of malignant ventricular arrhythmias was 6 and 9%, respectively. In multivariate analysis, a risk factor for SCD was left ventricular dysfunction. The annual heart failure rate was low at 0.5%; four patients died, two had heart transplants and one tricuspid reconstruction. Intrathoracic cardioverter-defibrillator (ICD) therapy was initiated in 35 patients. Adequate shocks after 6-72 months were delivered in 77%; in the majority aborted sudden death with documented ventricular fibrillation and unstable ventricular tachycardia were underlying arrhythmias., Conclusions: The clinical course of ARVD/C is characterized by a high rate of recurrent malignant ventricular arrhythmias in initially symptomatic and high-risk cases, and is uneventful in primarily asymptomatic affected individuals. The spectrum of clinical symptoms represents a warning symptom initiating the so-called 'hot phase' of the disease in many cases. ICD treatment is highly effective in cases of aborted SCD and unstable ventricular tachycardia.

Background: The use of electrocardiographic (ECG) depolarization and repolarization criteria plays a large role in the diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). Different ECG algorithms should be analyzed in making the diagnosis of ARVD/C with the use of normal and modified recording techniques., Methods: In a cohort of 343 patients (210 men and 133 women; mean age, 46.0 +/- 13.7 years) meeting the Task Force of the Working Group on Myocardial and Pericardial Diseases of the European Society of Cardiology and the Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology diagnostic criteria for ARVD/C, the value of different ECG criteria (eg, localized right precordial QRS prolongation defined as QRS duration in (V1+V2+V3)/(V4+V5+V6) of 1.2 or higher, right precordial QRS prolongation with QRS in V1-3 of 110 milliseconds or higher, epsilon potentials in the right precordial leads, S-wave upstroke in V1-3 of 55 milliseconds or higher, and right precordial T-wave inversions) was analyzed with the use of a normal recording technique and a highly amplified and modified recording technique (n = 207) at a paper speed of 50 mm/s. Fifty-two phenotypically and genotypically unaffected individuals identified by systematic screening in 24 families (30 men; mean age, 42.4 +/- 8.3 years) were treated as control subjects., Results: In the normal as well as highly amplified and modified recording techniques, the incidence of localized right precordial QRS prolongation was 98% (100%), that of QRS in V1-3 of 110 milliseconds or higher was 75% (80%), that of prolonged right precordial S-wave upstroke was 84% (60%), that of epsilon potentials was 23% (77%), and that of right precordial T-wave inversions was 55%. Four of 6 patients without the phenomenon of localized right precordial QRS prolongation with the use of the normal recording technique had a prolonged S-wave upstroke of 55 milliseconds or higher. In the control group, localized right precordial QRS prolongation, QRS in V1-3 of 110 milliseconds or higher, and epsilon potentials could not be identified. An S-wave upstroke of 55 milliseconds or higher was present in 2 of 3 cases, and T-wave inversions were found in 3., Conclusions: Electrocardiographic depolarization criteria for ARVD/C analyzed in this large cohort of patients meeting the International Society and Federation of Cardiology/European Society of Cardiology criteria presented with high sensitivity and specificity in comparison with those in the control group of phenotypically and genotypically unaffected individuals defined by systematic screening in 24 families with ARVD/C. The incidence of right precordial T-wave inversions was much lower, indicating that not only patients with overt right ventricular dilatation and dysfunction were included. Electrocardiographic algorithms, including localized right precordial QRS prolongation, prolonged S-wave upstroke, and epsilon potentials, with the use of the normal recording technique and the amplified and modified recording technique at a paper speed of 50 mm/s contribute significantly to the noninvasive diagnosis of ARVD/C.

Latest advances in the diagnostic management of arrhythmogenic right ventricular dysplasia-cardiomyopathy (ARVD/C) confirm that ARVD/C is not a rare disease (one affected in 1000-1250 inhabitants) and is of familial origin in 50-80% of cases. Diagnostic criteria defined in 1994 lead to low rates in the diagnosis of ARVD/C. Progress was made in the definition of diagnostic markers. New criteria of localised right precordial QRS prolongation could be identified. The detection of epsilon potentials could be enhanced by highly amplified and modified recording techniques. Vectorcardiography, signal averaging per lead and electroanatomic voltage mapping might become more important in the future. Cardiac MRI does not represent the single diagnostic test to make the diagnosis of ARVD/C. It remains a promising noninvasive imaging technique with advantages in the evaluation of the right ventricle. After the characterisation of mutations in the plakophilin-2 gene, molecular genetics is going to become an important diagnostic tool. Up to now, unsolved problems exist in the differentiation of ARVD/C and other conditions with ventricular arrhythmias evolving from the right ventricle such as Brugada syndrome and right ventricular outflow tract tachycardia. These problems can be overcome by distinct ECG analysis and the use of imaging techniques. With the help of corrected and modified diagnostic criteria it seems to be possible to identify symptomatic and asymptomatic affected by ARVD/C with predominantly major criteria and only in a minority of cases minor criteria.

Objective: Mutations in the cardiac ryanodine receptor (RYR2) gene have been reported to cause arrhythmogenic right ventricular cardiomyopathy (ARVC). The molecular mechanisms by which genetic modifications lead to ARVC are still not well understood., Methods: ARVC patients were screened for mutations in the RYR2 gene by denaturing HPLC and DNA sequencing. Single channel measurements were carried out with RyR2 channels purified from explanted hearts of ARVC patients., Results: None of the published RYR2 mutations were found in our ARVC-cohort. However, we identified two single nucleotide polymorphisms (SNPs) in exon 37 of the human RYR2 gene which lead to the amino acid exchanges G1885E and G1886S, respectively. Both SNPs together were found exclusively in 3 out of 85 ARVC patients in a composite heterozygous fashion (genotype T4). This genotype was associated with ARVC (p<0.05) but not with dilated cardiomyopathy (DCM, 79 patients) or none-failing controls (463 blood donors). However, either one of the two SNPs were identified in further 7 ARVC patients, in 11 DCM patients, and in 64 blood donors. The SNP leading to G1886S may create a protein kinase C phosphorylation site in the human RyR2. Single channel recordings at pCa4.3 revealed four conductance states for the RyR2 of genotype T4 and a single open state for the wild type RyR2. At pCa7.7, the lowest subconductance state of the RyR2 channel of genotype T4 persisted with a greatly enhanced open probability indicating a leaky channel., Conclusion: The RyR2 channel leak under diastolic conditions could cause SR-Ca2+ depletion, concomitantly arrhythmogenesis and heart failure in a subgroup of ARVC patients of genotype T4. A change in the RyR2 subunit composition due to the combined expression of both SNPs alters the behaviour of the tetrameric channel complex.

Syncopes appear in 10-20% in arrhythmogenic right ventricular dysplasia-cardiomyopathy (ARVD/C). In the majority of cases sustained or non-sustained monomorphic ventricular tachycardias represent the underlying mechanism of syncope. In other cases the mechanism remains unclear. In 37 patients (23 females, mean age 43.6+/-12.8 years) without detectable and inducible monomorphic ventricular tachycardia, a diagnostic algorithm including repeat ECG, holter monitoring, telemetry, electrophysiological examination, ajmaline challenge, tilt table testing and neurological work-up (EEG, cranial computer tomography) was used in order to identify the mechanism of syncopes. Constant AV block 3 degrees could be found in 3 patients (2 males). Intermittant AV block 2 degrees or 3 degrees could be identified in 3 females. Four males had abnormal Wenckebach point during rapid atrial stimulation, 3 males demonstrate isolated HV interval prolongation. Rapid polymorphic VT and VF could be induced in a young female with ARVD/C. Eight patients (7 females) presented with recurrent syncopes and provocable right precordial ST elevation and right bundle branch block during ajmaline challenge. Three patients had abnormal tilt table testing as the only pathological finding. In one female with intermittent AV block 2 degrees tilt table testing and ajmaline challenge was positive. One female had the diagnosis of focal epilepsia after neurological work-up. In 11 cases the mechanism of syncopes remained unclear. In patients with ARVD/C and syncopes beyond detectable or inducible monomorphic VT, several mechanisms of syncopes could be identified with conduction disease as the predominant finding. These results may help in identifying rare mechanisms of syncopes in ARVD/C.

In a cardiological department of a non-referral hospital responsible for 80,000 inhabitants with 2500 in-hospital patients and 1500 out-hospital patients per year, the prevalence, symptoms and prognosis of arrhythmogenic right ventricular dysplasia-cardiomyopathy (ARVD/C) were examined retrospectively. From 1997 to 2002, ARVD/C was diagnosed in 35 females and 45 males (overall prevalence 1 in 1000 inhabitants) with a mean age of 45.6 years. Symptoms were chest pain (80%), palpitations (60%) and syncopes (30%), and clinical findings were repetitive ventricular premature beats (50%), supraventricular arrhythmias (30%), ventricular tachycardia (20%), aborted sudden death due to ventricular fibrillation (1%), right heart failure (4%), biventricular heart failure (1%) and high grade AV nodal block (4%). Endomyocardial biopsies were not performed. Aborted sudden death occurred in only one patient (0.3%) before the diagnosis was made, annual heart failure rate was 1%. No deaths appeared in a follow-up of 1-5 (mean 2.4) years with clinical assessment as the basis of diagnosis. The prevalence of ARVD/C is much higher and the prognosis better than expected from results of reference centers.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with fibrofatty replacement of cardiac myocytes, ventricular tachyarrhythmias and sudden cardiac death. In 32 of 120 unrelated individuals with ARVC, we identified heterozygous mutations in PKP2, which encodes plakophilin-2, an essential armadillo-repeat protein of the cardiac desmosome. In two kindreds with ARVC, disease was incompletely penetrant in most carriers of PKP2 mutations.

An association between arrhythmogenic right ventricular dysplasia-cardiomyopathy (ARVD/C) and Brugada syndrome can be supposed according to several case reports. In order to examine a possible link between ARVD/C and Brugada syndrome, systematic ajmaline testing with 1 mg/kg body weight intravenously, was done in 55 patients (32 males, mean age 46.7+/-12.3 years) with ISFC/ESC criteria of ARVD/C. In nine patients ajmaline testing could demonstrate coved ST segment elevation of at least 2 mm in at least two right precordial leads. Three of these patients had recurrent syncopes. Electrophysiological study revealed non-sustained ventricular tachycardia with left bundle branch block configuration and inferior axis in only one case. Systematic ajmaline testing could demonstrate a definite link between ARVD/C and Brugada syndrome.

Background: The diagnostic dilemma in arrhythmogenic right ventricular dysplasia-cardiomyopathy (ARVD/C) is that a single diagnostic test does not exist and that there is a need for broadening diagnostic criteria. As standard ECG contributes significantly to clinical diagnosis and represents a tool for screening in family studies ECG data should be revisited., Methods and Results: In a cohort of 265 patients (159 males, mean age 46.8 years) with ISFC/ESC criteria of ARVD/C ECG features were reevaluated. QRS duration in (V1 + V2 + V3)/(V4 + V5 + V6) > or = 1.2-called localized right precordial QRS prolongation-was present in 261/265 patients (98%) and represents the essential finding. Right precordial epsilon potentials were found in 23% in standard and in 75% in highly amplified and modified recording technique. Right precordial T wave inversions were present in 143 cases (54%) and ST-segment elevation of different types in 66 patients (25%). Localized prolongation of inferior QRS complexes could be found in 58 cases (22%), complete right bundle branch block with T inversions beyond V2 in most cases in 17 patients (6%), incomplete right bundle branch block in 38 cases (14%), pseudo-incomplete right bundle branch block in 8 patients (3%), and right precordial R wave reduction in 14 cases (5%)., Conclusion: With regard to sensitivity and already known specificity an ECG score for the diagnosis of ARVD/C was developed with high probability of ARVD/C in cases with > or =4 points, possibly without the need for an additional imaging technique. Standard ECG with additional highly amplified and modified recording technique represents a single diagnostic test with high value in the clinical diagnosis of ARVD/C and should be used as a first line tool in noninvasive family screening.

The value of imaging techniques such as transthoracic echocardiography, angiography and magnetic resonance imaging in the diagnosis of arrhythmogenic right ventricular dysplasia-cardiomyopathy (ARVD) is limited. First experiences with intracardiac ultrasound have been made during electrophysiological interventions. The ability of using intracardiac ultrasound in ARVD should be tested. In 25 patients with IFSC/ESC criteria of ARVD (nine males, 16 females) with a mean age of 54 (29-78) years suffering from sustained ventricular tachycardia in three cases, positive family history in four cases and syncopes in six cases intracardiac ultrasound was done using 6 French (Fr) 12.5 MHz catheters and the CLEAR VIEW ULTRA Intravascular System (Boston Scientific). Images were taken from the right ventricular apex, outflow tract and infundibulum. Results were compared to selective right ventricular angiography. Right ventricular (RV) angiography revealed bulges and a partial or complete loss of trabecular structure in 22 cases at the apex, in 13 cases at the infundibulum and in 14 cases at the right ventricular outflow tract. Intracardiac echocardiography was able to demonstrate sacculations in all patients at the apex, in 20 cases at the infundibulum and in 16 patients at the right ventricular outflow tract. Sacculations in all segments of the right ventricle were based on a partial or complete loss of trabecular structure. A whole of 36 segments presented with wall thinning (<3 mm) and 15 segments with normal wall structure and wall thickening of surrounding myocardium (>4 mm). In 26 segments the structure of right ventricular wall was inhomogeneous. In comparison to angiography as the 'gold standard' intracardiac ultrasound presented with additional details in 12 cases and the demonstration of angiographic misinterpretation in one case. Intracardiac ultrasound in ARVD is feasible in all cases with 6 Fr 12.5 MHz catheters and provides additional information to the angiographic phenomenon of bulges and to the aspect of tissue characterisation.

The so-called Brugada syndrome (BS), first called precordial early repolarization syndrome (PERS), is characterized by the association of a fascinating electrocardiographic pattern, namely an aspect resembling right bundle branch block with a coved and sometime upsloping ST segment elevation in the precordial leads, and major ventricular arrhythmic events that could rarely lead to sudden death. Its electrogenesis has been related to a conduction delay mostly, but not only, located on the right ventricular outflow tract (RVOT), probably due to a progressive fibrosis of the conduction system. Many tests have been proposed to identify people at risk of sudden death and, among all, ajmaline challenge, thanks to its ability to enhance latent conduction defects, became so popular, even if its role is still controversial as it is neither specific nor sensitive enough to guide further invasive investigations and managements. Interestingly, a type 1 pattern has also been induced in many other cardiac diseases or systemic diseases with a cardiac involvement, such as long QT syndrome (LQTS), arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM) and myotonic dystrophy, without any clear arrhythmic risk profile. Evidence-based studies clearly showed that a positive ajmaline test does not provide any additional information on the risk stratification for major ventricular arrhythmic events on asymptomatic individuals with a non-diagnostic Brugada ECG pattern. [ABSTRACT FROM AUTHOR]

Over the past decades, there has been tremendous progress in understanding genetic alterations that can result in different phenotypes of human cardiomyopathies. More than a thousand mutations in various genes have been identified, indicating that distinct genetic alterations, or combinations of genetic alterations, can cause either hypertrophic (HCM), dilated (DCM), restrictive (RCM), or arrhythmogenic cardiomyopathies (ARVC). Translation of these results from "bench to bedside" can potentially group affected patients according to their molecular etiology and identify subclinical individuals at high risk for developing cardiomyopathy or patients with overt phenotypes at high risk for cardiac deterioration or sudden cardiac death. These advances provide not only mechanistic insights into the earliest manifestations of cardiomyopathy, but such efforts also hold the promise that mutation-specific pathophysiology might result in novel "personalized" therapeutic possibilities. Recently, the FLNC gene encoding the sarcomeric protein filamin C has gained special interest since FLNC mutations were found in several distinct and possibly overlapping cardiomyopathy phenotypes. Specifically, mutations in FLNC were initially only linked to myofibrillar myopathy (MFM), but are now increasingly found in various forms of human cardiomyopathy. FLNC thereby represents another example for the complex genetic and phenotypic continuum of these diseases. [ABSTRACT FROM AUTHOR]