Mechanisms of torsade de pointes tachycardia in patients with spontaneous high-degree atrioventricular block: A modern look at old data.

INTRODUCTION: The mechanisms of torsade de pointes tachycardia (TdP) are incompletely understood. We aimed to investigate the mechanisms underlying TdP tachycardia in patients with spontaneous high-degree atrioventricular block (AVB). METHODS AND RESULTS: This retrospective study reviewed old TdP recordings after ventricular temporary pacing interruption in 16 patients with spontaneous high-degree AVB. Five of them had also bipolar endocardial right ventricular (RV) apex recordings. The QT interval during AVB at a mean heart rate of 38.9 ±â€¯7.5 bpm was 653.0 ±â€¯67.2 ms. The critical coupling interval (CCI) between the last escape QRS during AVB and the first premature ventricular complex (PVC) was significantly shorter before the onset of TdP than before single PVCs and couplets. A morphologic crescendo of the escape T wave was observed before the onset of TdP, followed by a rhythmic and morphologic crescendo of PVCs. The escape RV apex electrograms (EGMs) showed the constant pattern of a rapid deflection similar to a Purkinje potential 40 to 80 ms after the onset of the QRS, superimposed on a smooth low amplitude signal in 4 out of 5 patients. CONCLUSIONS: The major endocardial T wave prolongation and augmentation (morphologic crescendo) of the escape beat prior to the first PVC suggests a phase 2 reentry mechanism due to early afterdepolarization. The induced TdP can be due to the changing outputs from one or two simultaneous RV moving reentry circuits between depressed fibers and fast conducting ones, possibly located in the thin crista supraventricularis structure which has several connections with the septum and the RV free wall.

Value of a novel 16-lead High-Definition ECG machine to detect conduction abnormalities in structural heart disease.

BACKGROUND: Depolarization abnormalities are hardly detectable by standard 12-lead electrocardiogram (ECG) in some patients. OBJECTIVE: To evaluate the value of the 16-lead High-Definition (HD)-ECG machine to record conduction abnormalities including Epsilon waves in patients with structural heart disease. METHODS: Tracings with 12-lead ECG, 16-lead HD-ECG, and signal-averaged ECG were studied. RESULTS: (1) Case of severe coronary artery disease (CAD): On 16-lead HD-ECG, a tiny intra-QRS signal was noted in lead III, a prolonged P wave in lead II, and fragmentation on top of lead aVL and lead aVF. Proper automatic measurement of the prolonged P wave measuring 190 ms was noted. Signal-averaging by 16-lead HD-ECG in lead III showed the intra-QRS fragmentation and P wave prolongation of 180 ms. (2) First patient with arrhythmogenic right ventricular dysplasia (ARVD): Standard 12-lead ECG indicated Epsilon waves in lead III, V2, V3, and inverted T waves in V1-V3. 16-lead HD-ECG indicated QRS prolongation in lead II, III, aVL, aVF, V2, V3 as opposed to V6, and low amplitudes of QRS complexes in V4R and V3R as a new possible sign of ARVD. Notches in lead V2, widening of QRS complexes in all precordial leads, but shorter QRS in V8-V9 are also considered as a potential new diagnostic sign of ARVD. (3) Second ARVD patient: Notches at the end of the QRS in lead III and a negative initial deflection of the QRS in V1 and V2 were detected by standard 12-lead ECG. On 16-lead HD-ECG, a more pronounced QRS fragmentation was visible. CONCLUSION: 16-lead HD-ECG in both CAD and ARVD seems to be more sensitive than 12-lead ECG to record electrocardiographic abnormalities.

Epsilon waves: Milestones in the discovery and progress.

The Epsilon wave was first identified in 1977. Four decades of progress help people to better understand its pathological electrogenesis and diagnostic value. Currently, the Epsilon wave is on the list of the 2010 Task Force recommendations for the diagnosis of arrhythmogenic right ventricular dysplasia (ARVD). In this review, we provide the history of the first recording of the Epsilon wave in coronary artery disease and Uhl's anomaly, subsequently leading to the signal averaging technique to record late potentials. Based on our experience, we discuss some existing controversies. When we look back at the decades of progress of the Epsilon wave, we conclude that the Epsilon wave is only the tip of the iceberg of ECG abnormalities in ARVD.

Epsilon wave on an electronic loop in a case of arrhythmogenic right ventricular dysplasia with myocarditis: an updated definition of the Epsilon wave.

A young man presented with a history of myocarditis with palpitations and dizziness. He had implantation of a loop recorder that showed repetitive short episodes of VT. In addition, there were fragmented potentials immediately following the large and sharp electrograms (EGMs) before as well as after episodes of VT suggesting an Epsilon wave. This signal can be observed in multiple cardiac conditions including coronary artery disease. It was originally recorded on the epicardium as well as on the endocardium. However, in ARVD it can be defined as an electric signal observed after the end of the QRS complex in the right as opposed to the left precordial leads (difference ≥ 25 ms). It can also be an aid to the diagnosis of patients with ARVD who have other signs or symptoms suggesting ARVD including episodes of myocarditis. This potential consists of a slurring at the end of the QRS complex or an independent potential after the return to the isoelectric line. It can be better observed by increasing amplification of the ECG tracing as well as double speed using the Fontaine lead system. Epsilon wave too small to be recorded on the standard ECG can be extracted by Signal Averaging ECG SAECG).

The use of fontaine leads in the diagnosis of arrhythmogenic right ventricular dysplasia.

We report a case of a 68-year-old man admitted to the emergency department with syncope preceded by rapid palpitations. His admission ECG demonstrated a sustained ventricular tachycardia (VT) originating from the right ventricular outflow tract (RVOT). This report highlights the importance of distinguishing ventricular tachycardia caused by arrhythmogenic right ventricular dysplasia (ARVD) from the more benign idiopathic RVOT-VT. Furthermore, we demonstrate the utility of the Fontaine leads placement in increasing the sensitivity for uncovering epsilon waves, a highly specific electrocardiographic feature that increases diagnostic accuracy in patients with ARVD.

Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria.

BACKGROUND: In 1994, an International Task Force proposed criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and interpretation of the frequently nonspecific clinical features of ARVC/D. This enabled confirmatory clinical diagnosis in index cases through exclusion of phenocopies and provided a standard on which clinical research and genetic studies could be based. Structural, histological, electrocardiographic, arrhythmic, and familial features of the disease were incorporated into the criteria, subdivided into major and minor categories according to the specificity of their association with ARVC/D. At that time, clinical experience with ARVC/D was dominated by symptomatic index cases and sudden cardiac death victims-the overt or severe end of the disease spectrum. Consequently, the 1994 criteria were highly specific but lacked sensitivity for early and familial disease. METHODS AND RESULTS: Revision of the diagnostic criteria provides guidance on the role of emerging diagnostic modalities and advances in the genetics of ARVC/D. The criteria have been modified to incorporate new knowledge and technology to improve diagnostic sensitivity, but with the important requisite of maintaining diagnostic specificity. The approach of classifying structural, histological, electrocardiographic, arrhythmic, and genetic features of the disease as major and minor criteria has been maintained. In this modification of the Task Force criteria, quantitative criteria are proposed and abnormalities are defined on the basis of comparison with normal subject data. CONCLUSIONS: The present modifications of the Task Force Criteria represent a working framework to improve the diagnosis and management of this condition. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00024505.

Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria.

BACKGROUND: In 1994, an International Task Force proposed criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and interpretation of the frequently nonspecific clinical features of ARVC/D. This enabled confirmatory clinical diagnosis in index cases through exclusion of phenocopies and provided a standard on which clinical research and genetic studies could be based. Structural, histological, electrocardiographic, arrhythmic, and familial features of the disease were incorporated into the criteria, subdivided into major and minor categories according to the specificity of their association with ARVC/D. At that time, clinical experience with ARVC/D was dominated by symptomatic index cases and sudden cardiac death victims-the overt or severe end of the disease spectrum. Consequently, the 1994 criteria were highly specific but lacked sensitivity for early and familial disease. METHODS AND RESULTS: Revision of the diagnostic criteria provides guidance on the role of emerging diagnostic modalities and advances in the genetics of ARVC/D. The criteria have been modified to incorporate new knowledge and technology to improve diagnostic sensitivity, but with the important requisite of maintaining diagnostic specificity. The approach of classifying structural, histological, electrocardiographic, arrhythmic, and genetic features of the disease as major and minor criteria has been maintained. In this modification of the Task Force criteria, quantitative criteria are proposed and abnormalities are defined on the basis of comparison with normal subject data. CONCLUSIONS: The present modifications of the Task Force Criteria represent a working framework to improve the diagnosis and management of this condition. Clinical Trial Registration clinicaltrials.gov Identifier: NCT00024505.

Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice.

AIMS: Five desmosomal genes have been recently implicated in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) but the clinical impact of genetics remains poorly understood. We wanted to address the potential impact of genotyping. METHODS AND RESULTS: Direct sequencing of the five genes (JUP, DSP, PKP2, DSG2, and DSC2) was performed in 135 unrelated patients with ARVD/C. We identified 41 different disease-causing mutations, including 28 novel ones, in 62 patients (46%). In addition, a genetic variant of unknown significance was identified in nine additional patients (7%). Distribution of genes was 31% (PKP2), 10% (DSG2), 4.5% (DSP), 1.5% (DSC2), and 0% (JUP). The presence of desmosomal mutations was not associated with familial context but was associated with young age, symptoms, electrical substrate, and extensive structural damage. When compared with other genes, DSG2 mutations were associated with more frequent left ventricular involvement (P = 0.006). Finally, complex genetic status with multiple mutations was identified in 4% of patients and was associated with more frequent sudden death (P = 0.047). CONCLUSION: This study supports the use of genetic testing as a new diagnostic tool in ARVC/D and also suggests a prognostic impact, as the severity of the disease appears different according to the underlying gene or the presence of multiple mutations.

Fragmented endocardial signals and early afterdepolarizations during torsades de pointes tachycardia.

BACKGROUND: Bradycardia-induced torsade de pointes (TdP) tachycardia in patients with spontaneous high-degree atrioventricular block (AVB) is common. The aim of this study was to analyze endocardial recordings during TdP in spontaneous high-degree AVB in humans to better understand the electrophysiological mechanisms underlying this phenomenon. METHODS: The study group consisted of 5 patients with typical episodes of TdP during spontaneous high-degree AVB. A standard (USCI) temporary bipolar endocardial catheter positioned at the apex of the right ventricle (RV) and bipolar chest leads from two precordial leads V1 and V4 were used to record the tracings during TdP. RESULTS: The presence of a wide spectrum of fragmentations was noted on endocardial electrograms (EGMs), which were invisible on the surface electrocardiogram (ECG) tracing. Endocardial signals indicated that TdP started in the proximity of the RV apex, since the local EGM began prior to the QRS complex on the surface ECG. Early afterdepolarizations (EADs) were observed in 2 out of 5 cases confirming a common opinion about the mechanism of TdP. However, this phenomenon was not observed in 3 other patients suggesting that the arrhythmia was the result of a different mechanism originating in proximity to the RV apex. CONCLUSIONS: This work demonstrated early endocardial signals in the RV apex during TdP associated with high-degree AVB in humans, and exhibits a spectrum of fragmented signals in this area occurring on a single or multiple beats. These fragmentations indicate areas of poor conduction and various degrees of intramyocardial block, and therefore a new mechanism of TdP tachycardia in some patients with spontaneous high-degree AVB.

Characterization of a Canadian mink H3N2 influenza A virus isolate genetically related to triple reassortant swine influenza virus.

In 2007, an H3N2 influenza A virus was isolated from Canadian mink. This virus was found to be phylogenetically related to a triple reassortant influenza virus which emerged in Canadian swine in 2005, but it is antigenically distinct. The transmission of the virus from swine to mink seems to have occurred following the feeding of animals with a ration composed of uncooked meat by-products of swine obtained from slaughterhouse facilities. Serological analyses suggest that the mink influenza virus does not circulate in the swine population. Presently, the prevalence of influenza virus in Canadian farmed and wild mink populations is unknown. The natural occurrence of influenza virus infection in mink with the presence of clinical signs is a rare event that deserves to be reported.

Sporadic arrhythmogenic right ventricular cardiomyopathy/dysplasia due to a de novo mutation.

We report the case of a 41-year-old man with a diagnosis of sporadic arrhythmogenic right ventricular cardiomyopathy (ARVC). Genetic screening identified the heterozygous missense mutation R49H in the desmoglein-2 gene. The mutation was absent in both parents, and we demonstrated that it was a de novo mutation. To the best of our knowledge, this is the first description of a de novo mutation in ARVC. This has important implications, including for clinical practice, since individuals with sporadic ARVC caused by a de novo mutation can transmit the disease gene to 50% of their offspring. This suggests that the benefit of molecular genetics can be extended to sporadic ARVC and may improve genetic counselling.

Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (ARVC/D) - What We Have Learned after 40 Years of the Diagnosis of This Clinical Entity.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) was initially recognized as a clinical entity by Fontaine and Marcus, who evaluated a group of patients with ventricular tachyarrhythmia from a structurally impaired right ventricle (RV). Since then, there have been significant advances in the understanding of the pathophysiology, manifestation and clinical progression, and prognosis of the pathology. The identification of genetic mutations impairing cardiac desmosomes led to the inclusion of this entity in the classification of cardiomyopathies. Classically, ARVC/D is an inherited disease characterized by ventricular arrhythmias, right and / or left ventricular dysfunction; and fibro-fatty substitution of cardiomyocytes; its identification can often be challenging, due to heterogeneous clinical presentation, highly variable intra- and inter-family expressiveness, and incomplete penetrance. In the absence of a gold standard that allows the diagnosis of ARVC/D, several diagnostic categories were combined and recently reviewed for a higher diagnostic sensitivity, without compromising the specificity. The finding that electrical abnormalities, particularly ventricular arrhythmias, usually precede structural abnormalities is extremely important for risk stratification in positive genetic members. Among the complementary exams, cardiac magnetic resonance imaging (CMR) allows the early diagnosis of left ventricular impairment, even before morpho-functional abnormalities. Risk stratification remains a major clinical challenge, and antiarrhythmic drugs, catheter ablation and implantable cardioverter defibrillator are the currently available therapeutic tools. The disqualification of the sport prevents cases of sudden death because the effort can trigger not only the electrical instability, but also the onset and progression of the disease.

Atrial dysplasia in the atria of humans without cardiovascular disease.

Research on atrial histology of humans without cardiovascular disease is scarce. Therefore, our aim was to study human atrial histology in subjects without cardiovascular disease. Histology of the right atrium, left atrium or atrial septum was studied in eight patients (one newborn infant and seven adults) who died of a non-cardiac cause and who were not known to suffer from any cardiovascular pathology. Staining with hematoxylin phloxine saffron or Masson's trichrome was performed to have a better identification of fibrosis and H&E for better identification of lymphocytes. Atrial histology was compared with the histology of the left ventricle and was taken from a collection of standard glass slides. Common light microscopic examination and numeric image processing was performed in all samples. Left atrial histology showed a substantial amount of adipocytes and interstitial fibrosis, associated with replacement fibrosis in some of these cases including one case of lymphocytic infiltrates, similar to the histologic changes of the right ventricle (RV) known in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVD). Furthermore, we identified a perpendicular orientation of atrial myocardial fibres, which is also a feature of the thin RV free wall. A similar histologic substrate to the RV myocardium known in ARVD is found in the atria of humans without an overt cardiovascular pathology. This may explain the high prevalence of atrial fibrillation in the general population.

Right atrial pathology in arrhythmogenic right ventricular dysplasia.

BACKGROUND: Atrial fibrillation (AF) is the most common atrial arrhythmia in arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVD). Considering the histologic changes known in the right ventricular (RV) in ARVD, the aim of the present study was to examine right atrial (RA) pathology in patients with ARVD. METHODS: Histology of RA and RV was assessed from autopsy material in 3 patients with ARVD without persistent atrial arrhythmia. RA histology in 3 patients with permanent AF without ARVD and 5 patients without cardiovascular disease was also studied. Staining with hematoxylin phloxine saffron was performed for the ARVD patients to identify fibrosis, and hematoxylin-eosin for identification of lymphocytes. Masson's trichrome staining was performed for control groups taken from a collection of standard glass slides. RESULTS: In all 3 ARVD cases, RA anomalies were observed that revealed a reduction of cardiomyocytes, the presence of adipocytes, some of them inside the mediomural atrial layer and interstitial fibrosis. In 2 ARVD cases, interstitial fibrosis was also associated with a focus of replacement fibrosis, which was also observed in patients with permanent AF without ARVD. The histologic specimen of the RA and RV from the control group without cardiovascular disease did not display any evidence of fat or fibrosis with a preserved cardiomyocyte architecture. CONCLUSIONS: A similar histopathological substrate, as can be observed in the RV of patients with ARVD can also be seen in the RA of these patients. This may explain the high prevalence of atrial arrhythmias, particularly AF, in patients with ARVD.

Brugada syndrome in pure black Africans.

AIMS: Although all races are concerned with the Brugada syndrome, no case has ever been reported among black Africans. We describe five different cases in this specific group of populations. METHODS AND RESULTS: In all patients, Brugada syndrome was identified after detailed noninvasive and invasive evaluations. Sex ratio was four males for one female. Convulsive syncope was noticed in 1 patient with a family history of sudden death. Diagnostic coved-type pattern was observed spontaneously in the normal position of right precordial leads in 3 patients and in a higher position of leads in 3 patients. Sixty percent had first-degree atrioventricular block. An ajmaline test was performed in 4 patients and was positive either in normal position of leads or in superior position in all of them. Sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) was inducible during programmed ventricular stimulation in 3 patients. Right ventricular cineangiography found localized apical hypokinesia with preserved systolic function in 1 patient. Automatic cardioverter defibrillator was implanted in 2 patients. SCN5A was not found in any of the patients. CONCLUSION: These observations demonstrate that Brugada syndrome is also present in black African populations, and increasingly reported cases of apparent sudden death in the sub-Saharan part of the world need to rule out cardiac electrical disturbance such as Brugada syndrome.

Clinical experience with a low-energy pulsed biphasic waveform in out-of-hospital cardiac arrest.

The efficiency of a pulsed biphasic waveform (PBW) was compared with that of biphasic truncated exponential (BTE) waveforms. First defibrillation shock outcome was studied in a population of 104 out-of-hospital cardiac arrest patients in ventricular fibrillation as the presenting rhythm. The call to first shock time was 8.2+/-5.4 min. At 5s post-shock, defibrillation efficiency was 90%. The arrest was witnessed in only 50% of the patients and only 5% received bystander CPR. Despite these limitations 38% of the patients achieved restoration of a spontaneous circulation at departure from scene and 9.8% were discharged from the hospital. These observations demonstrate a rate of first shock success in termination of ventricular fibrillation comparable to that reported with biphasic truncated exponential waveforms in out-of-hospital cardiac arrest.

Development and use of a multiplex real-time quantitative polymerase chain reaction assay for detection and differentiation of Porcine circovirus-2 genotypes 2a and 2b in an epidemiological survey.

By the end of 2004, the Canadian swine population had experienced a severe increase in the incidence of Porcine circovirus-associated disease (PCVAD), a problem that was associated with the emergence of a new Porcine circovirus-2 genotype (PCV-2b), previously unrecovered in North America. Thus, it became important to develop a diagnostic tool that could differentiate between the old and new circulating genotypes (PCV-2a and PCV-2b, respectively). Consequently, a multiplex real-time quantitative polymerase chain reaction (mrtqPCR) assay that could sensitively and specifically identify and differentiate PCV-2 genotypes was developed. A retrospective epidemiologic survey that used the mrtqPCR assay was performed to determine if cofactors could affect the risk of PCVAD. From 121 PCV-2-positive cases gathered for this study, 4.13%, 92.56%, and 3.31% were positive for PCV-2a, PCV-2b, and both genotypes, respectively. In a data analysis using univariate logistic regressions, the PCVAD-compatible (PCVAD/c) score was significantly associated with the presence of Porcine reproductive and respiratory syndrome virus (PRRSV), PRRSV viral load, PCV-2 viral load, and PCV-2 immunohistochemistry (IHC) results. Polytomous logistic regression analysis revealed that PCVAD/c score was affected by PCV-2 viral load (P = 0.0161) and IHC (P = 0.0128), but not by the PRRSV variables (P > 0.9), which suggests that mrtqPCR in tissue is a reliable alternative to IHC. Logistic regression analyses revealed that PCV-2 increased the odds ratio of isolating 2 major swine pathogens of the respiratory tract, Actinobacillus pleuropneumoniae and Streptococcus suis serotypes 1/2, 1, 2, 3, 4, and 7, which are serotypes commonly associated with clinical diseases.

Endomyocardial biopsy in patients with acute myocarditis, idiopathic dilated cardiomyopathy, and arrhythmogenic right ventricular dysplasia.

Endomyocardial biopsy (EMB) is useful for the diagnosis of myocarditis, cardiac sarcoidosis, and non-ischemic cardiomyopathy. In this mini-review, we discuss the diagnostic potential of EMB in cases of acute/chronic-active myocarditis, sarcoidosis, idiopathic dilated cardiomyopathy and arrhythmogenic right ventricular dysplasia. We also summarize the complications caused by endomyocardial biopsy procedures. Importantly, we finally review the emerging molecular biology technologies as well as biological engineering techniques that can help improve the diagnostic accuracy of EMB to diagnose myocarditis and cardiomyopathies, promoting the management of these diseases.