Epsilon Waves Research Articles

The precordial R-prime wave: a novel discriminator between cardiac sarcoidosis and arrhythmogenic right ventricular cardiomyopathy in patients presenting with ventricular tachycardia

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): The department of cardiology from Leiden University Medical Center receives unrestricted grants from Edwards Lifesciences, Biotronik, Medtronik, Boston Scientific and BioSense Webster. MS was supported by the Research Fellowship of the European Society of Cardiology 2017/2018. Background Cardiac sarcoidosis (CS) with right ventricular (RV) involvement may mimic ARVC. Histopathological differences may result in disease specific RV activation patterns, detectable on the 12-lead electrocardiogram (ECG). Scar in ARVC progresses from epicardium to endocardium and may lead to delayed activation of areas with reduced voltages, translating into terminal activation delay and occasionally an (epsilon) wave with small amplitude on the ECG. On the contrary, patchy transmural RV scar in CS may lead to conduction block, and therefore late activated areas with preserved voltages, reflected as preserved R’-waves in the right precordial leads. Purpose To determine whether the terminal activation patterns in precordial leads V1-V3 distinguish CS with RV involvement from ARVC. Methods This is a multicenter retrospective study including patients with either 1) CS with RV involvement or 2) gene-positive ARVC referred for VT ablation. A non-ventricular paced 12-lead surface ECG prior to ablation was obtained (25mm/s and 10mm/mV). For detailed analysis, Leiden ECG Analysis and Decomposition Software (LEADS) was used. After detection of QRST complexes in the spatial velocity signal, LEADS generates a representative and low-noise averaged beat. Then, measurements per lead were performed using the measurement tool in Adobe Pro DC. Based on the hypothesis that conduction block in CS will lead to late activated areas with preserved voltages, we measured the surface area (SA) of the R’-wave in V1-V3. An R’-wave was defined as any positive deflection from baseline after an S-wave. Results 13 CS patients with RV involvement (54 ± 8years, 62% male) and 23 ARVC patients (37 ± 15years, 78% male) were included. A R’-wave in V1-V3 was present in all CS patients, compared to 11 (48%) of ARVC patients (p = 0.002). The maximum R’-wave SA in lead V1-V3 was 3.55 (IQR:2.18-5.81) mm2 in CS vs. 0.00 (IQR:0.00-0.43) mm2 in ARVC (p < 0.001; Figure A). By ROC-analysis, the maximum R’-wave SA in lead V1-V3 was an excellent discriminator (area under the curve 0.980 [95%CI: 0.945-1.000]). A cutoff of ≥1.65mm2 had a sensitivity of 85% and specificity of 96% for diagnosing CS. An algorithm was created including the presence of an R’-wave in V1-V3 and the SA of this R’-wave (Figure B). This was validated in a second cohort (18 CS and 40 ARVC) with 72% sensitivity and 88% specificity. Conclusion Transmural RV scars in CS may cause localized conduction block, leading to late activated areas with preserved voltages, reflected as large R’-wave on the 12-lead surface ECG. An easily applicable algorithm including the surface area of the largest R’-wave in lead V1-V3 ≥1.65mm2 distinguishes CS from ARVC with good sensitivity and specificity. The QRS terminal activation in precordial leads V1-V2 may reflect disease specific scar patterns (for examples: Figure C). Abstract Figure

Analysis of DSG2, TTN and GATA4 gene variants in patients with Brugada syndrome from Henan

To explore the correlation between DSG2, TTN and GATA4 genes and Brugada syndrome in Henan Province of China. From February 2017 to February 2019, 100 patients with Brugada syndrome and 100 healthy individuals were selected as the study and the control groups, respectively. Electrocardiogram and echocardiography were carried out, and peripheral blood samples was collected. Coding regions of DSG2, TTN and GATA4 genes were amplified by PCR and sequenced. The results were compared with standard sequences from GenBank. Electrocardiogram showed that all patients from the study group had ventricular arrhythmia, 87 cases (87%) presented ventricular tachycardia (VT), 84 cases (84%) presented T wave inversion, and 51 cases (51%) presented Epsilon wave. Echocardiography showed that the right ventricle in the study group was enlarged with the inner diameter of the right ventricle being (40.0±13.3) mm, and the right ventricle showed various degree of abnormal systolic function. The enlargement of right atrium accounted for 64%, and the involvement of the left ventricle accounted for 27%. The right ventricular diameter and left ventricular diastolic diameter of the study group were significantly greater than those of the control group (P< 0.05). DNA sequencing showed that 60 patients carried DSG2 gene variants, among which 18 had missense variant of exon 8. Fifty patients carried TTN gene variants, including 8 in the A-band domain and 3 in the I-band domain. Twenty patients carried 3 variants of the GATA4 gene. Variants of the DSG2, TTN and GATA4 genes in Henan region are correlated with the onset of Brugada syndrome.

The precordial R' wave: A novel discriminator between cardiac sarcoidosis and arrhythmogenic right ventricular cardiomyopathy in patients presenting with ventricular tachycardia.

Cardiac sarcoidosis (CS) with right ventricular (RV) involvement can mimic arrhythmogenic right ventricular cardiomyopathy (ARVC). Histopathological differences may result in disease-specific RV activation patterns detectable on the 12-lead electrocardiogram. Dominant subepicardial scar in ARVC leads to delayed activation of areas with reduced voltages, translating into terminal activation delay and occasionally (epsilon) waves with a small amplitude. Conversely, patchy transmural RV scar in CS may lead to conduction block and therefore late activated areas with preserved voltages reflected as preserved R' waves. The purpose of this study was to evaluate the distinct terminal activation patterns in precordial leads V1 through V3 as a discriminator between CS and ARVC. Thirteen patients with CS affecting the RV and 23 patients with gene-positive ARVC referred for ventricular tachycardia ablation were retrospectively included in a multicenter approach. A non-ventricular-paced 12-lead surface electrocardiogram was analyzed for the presence and the surface area of the R' wave (any positive deflection from baseline after an S wave) in leads V1 through V3. An R' wave in leads V1 through V3 was present in all patients with CS compared to 11 (48%) patients with ARVC (P=.002). An algorithm including a PR interval of ≥220 ms, the presence of an R' wave, and the surface area of the maximum R' wave in leads V1 through V3 of ≥1.65 mm2 had 85% sensitivity and 96% specificity for diagnosing CS, validated in a second cohort (18 CS and 40 ARVC) with 83% sensitivity and 88% specificity. An easily applicable algorithm including PR prolongation and the surface area of the maximum R' wave in leads V1 through V3 of ≥1.65 mm2 distinguishes CS from ARVC. This QRS terminal activation in precordial leads V1 through V3 may reflect disease-specific scar patterns.

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.

Abstract 13144: Epsilon Waves on Electrocardiograms in Pulmonary Hypertensive Patients With and Without Right Ventricular Hypertrophy or Fibrosis: Comparison With Arrhythmogenic Right Ventricular Cardiomyopathy

Introduction: Epsilon waves on V1-3 leads are one of the specific ECG findings in patients with arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC) that suggest the presence of RV conduction delay. Hypothesis: In patients with pulmonary hypertension (PH) due to RV pressure load, RV hypertrophy and fibrosis are frequently observed that may lead to RV conduction delay and epsilon waves. Methods: We retrospectively analyzed 43 PH patients (33 females, 55 ± 15 years, 31 chronic thromboembolic PH, seven idiopathic pulmonary arterial hypertension), with proven PH by right heart catheterization. On CT, RV fibrosis was defined as a contrast defect in the early phase and a conversely abnormal enhancement in the late phase. We also retrospectively analyzed 17 patients (11 males, 57 ± 17 years) with suspected ARVC who underwent cardiac CT. Of these, nine met 2010 ARVC task force criteria on cardiac CT. Results: All 9 ARVC patients (100%) had epsilon waves on ECG. In PH patients, 32 and 9 patients had RV hypertrophy and fibrosis, respectively. Of these, 4 patients had both. Among 32 PH patients with RV hypertrophy, 2 had complete right bundle branch block (RBBB) and 8 had incomplete RBBB. Of 22 PH patients with RV hypertrophy but without any RBBB, two (9%, P &lt; 0.01, compared with ARVC) had waves with abnormal small upward spikes after the QRS wave. These were more marked in lead II and aVF leads than in V1 and 2 leads, and were not typical epsilon waves, suggesting RV conduction delay shown in ARVC. Fourteen patients had a negative T wave in V1-3 leads (5 had only a V1 lead, one had only V1 and 2 leads, four had only V1-3 leads, and four only had V1-4 leads, respectively). Of nine PH patients with RV hypertrophy, one had complete RBBB and one had incomplete RBBB. Of seven PH patients with RV fibrosis but without any RBBB, none (0%, P &lt; 0.01, compared with ARVC) had epsilon waves in V1-3 leads; all seven had a negative T wave in V1-3 leads (three only had a V1 lead, one had only V1 and 2 leads, two had only V1-3 leads, and one had V1-4 leads). Conclusions: In PH patients with an organized RV myocardial change, such as RV hypertrophy and/or fibrosis, the frequency of epsilon waves was significantly less than those in ARVC. Epsilon waves seem not only to be caused by an organized RV myocardium but also by other factors.

Abstract 13084: Epsilon Waves on Electrocardiograms in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy: Relationship to Left Ventricular Invasion or Heart Compression Due to an Enlarged Right Ventricle

Introduction: Epsilon waves on V1-3 leads are known as one of the specific lead ECG findings in patients with arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC) that suggests the presence of RV conduction delay. Four dimensional (4D) cardiac CT visualizes ARVC characteristics, such as fat and fibrotic invasion in RV (RVM) and left ventricular (LV) myocardium (LVM), an enlarged RV, reduced RV motion, and bulging. Hypothesis: If epsilon waves are observed in V4-6 leads, this finding suggests the occurrence of LV invasion in ARVC. Another hypothesis exists in which extreme RV enlargement may compress the LV and cause clockwise rotation; an enlarged RV itself may cause epsilon waves in V4-6 leads. Methods: This is a retrospective analysis of 17 patients (11 males, 57 ± 17 years) with suspected ARVC who underwent cardiac CT. On 4D CT, nine met 2010 ARVC task force criteria. Results: All nine patients had epsilon waves on ECG. Five had fat and fibrotic invasion in the LVM but four did not. We divided nine into the following five groups by CT findings. On CT, a markedly enlarged RV compressed the LV to the left side and a fibro fatty change were observed exclusively in RVM (gp 1, N=1) or were observed in both RVM and LVM (gp 2, N=2). A moderately enlarged RV without compression of the LV to the left side and a fibro fatty change were observed exclusively in RVM (gp 3, N=3), or observed in both RVM and LVM (gp 4, N=2). The complications of severe mitral valve regurgitation, a markedly enlarged LV, and a fibro fatty change were observed in both RVM and LVM (gp 5, N=1). A patient in gp 1 showed epsilon waves in V1-6 leads. Patients in gp 2 showed epsilon waves in V1-6 (N=1), and V3-5 (N=1) leads, respectively. Patients in gp 3 showed epsilon waves in V1-4 (N=2), and V1-3 (N=1) leads, respectively. Patients in gp 4 showed epsilon waves in V1-3 (N=1), and V1, 2 (N=1) leads, respectively. A patient in gp 5 showed epsilon waves in V4-6 leads. Conclusions: The distribution of epsilon waves on ECG in patients with confirmed ARVC by cardiac CT was highly influenced by the degree of LV compression due to a markedly enlarged RV on CT rather than the presence of LV invasion. Also, structural change due to complicated heart diseases, such as valvular diseases, may also influence the distribution of epsilon waves in ARVC.

Abstract 13068: Epsilon and Inverted T Waves in Right Side Precordial Leads in Pulmonary Hypertensive Patients With or Without Right Ventricular Hypertrophy or Fibrosis on Cardiac Computed Tomography

Introduction: Epsilon and inverted T waves on V1-3 leads are known as specific ECG findings in patients with arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC), which suggests the presence of RV conduction delay. Right bundle branch block (RBBB) is often observed in ARVC. In patients with pulmonary hypertension (PH) due to RV pressure load, the occurrence of RV hypertrophy and fibrosis are frequently observed, which may also lead to the occurrence of RV conduction delay and epsilon waves. Hypothesis: We hypothesized that there were epsilon and inverted T waves in right side precordial leads on ECG in PH patients with RV hypertrophy and/or RV fibrosis, both confirmed on cardiac CT. Methods: We retrospectively analyzed 43 patients (33 females, 55 ± 15 years, 31 chronic thromboembolic PH, 7 idiopathic pulmonary arterial hypertension) with proven PH by right heart catheterization. On CT, RV fibrosis was defined as a contrast defect in the early phase and a conversely abnormal enhancement in the late phase. Results: 32 and 9 patients had RV hypertrophy and RV fibrosis, respectively; of these, 4 had both. Of 32 PH patients with RV hypertrophy, 2 had complete RBBB and 8 had incomplete RBBB. Of 22 PH patients with RV hypertrophy but without any RBBB, only one (5%) had typical epsilon waves and 2 (9%) had waves with abnormal small upward spikes after the QRS wave that were more marked in II and aVF leads than V1 and 2 leads; these were not typical epsilon waves. 14 had a negative T wave in V1-3 leads (5 had only a V1 lead, one had only V1 and 2 leads, 4 had only V1-3 leads, and 4 had V1-4 leads, respectively). Of 9 PH patients with RV hypertrophy, one had complete RBBB and one had incomplete RBBB. Of 7 PH patients with RV fibrosis but without any RBBB, none (0%) had epsilon waves in V1-3 leads. All 7 had a negative T wave in V1-3 leads (3 had only a V1 lead, one had only V1 and 2 leads, 2 had only V1-3 leads, and one had V1-4 leads). Conclusions: In a total of 37 PH participants with an organized RV myocardial change, such as RV hypertrophy and fibrosis confirmed on cardiac CT, only one (3%) had typical epsilon waves that are frequently found in patients with ARVC. The mechanism of epsilon waves occurring predominantly in V1-3 leads seems not only to be caused by an organised RV myocardium, but also by other factors.

Abstract 13073: ECG, Clinical, and Imaging Characteristics of Arrhythmogenic Right Ventricular Cardiomyopathy With Fat and Fibrotic Invasion Into the Left Ventricular Myocardium Revealed by Four-dimensional (4D) Cardiac CT

Introduction: 4D cardiac CT can reveal characteristics of arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC) such as fat and fibrotic invasion into the RV and LV myocardium (RVM, LVM), an enlarged RV, reduced RV motion and bulging. Hypothesis: We could differentiate ARVC patients with fat and fibrotic invasion into the LVM from those without, using ECG, clinical, and other imaging characteristics. Methods: Retrospective analysis of 17 patients (11 males, 57±17 years) with suspected ARVC who underwent 4D cardiac CT. Results: 9 patients met the 2010 ARVC task force criteria. 4 had fat and fibrotic invasion into the LVM (group 1) but 5 did not (group 2). The remaining 8 did not fulfill the ARVC criteria (group 3). The proportion of males and age did not differ between groups. In groups 1, 2 and 3, respectively, 3 (75%), 4 (80%), and 1 (13%) patients had epsilon waves in V1-3 (group 1&gt;3, P=0.033, group 2&gt;3, P=0.005). 2 (50%), one (20%) and 4 (50%) had complete right bundle branch block (CRBBB) (all P=NS). Three (75%), 3 (60%), and 1 (13%) had inverted T waves in V1-3 or beyond (group 1&gt;3, P=0.033). One (50%), 3 (75%), and 2 (50%) had terminal activation duration of QRS ≥55 ms measured from the nadir of the S wave to the end of the QRS, including R’, in V1, V2, or V3, in the absence of CRBBB (all P=NS). One (25%), 4 (80%) and 1 (13%) had sustained ventricular tachycardia (SVT; group 2&gt;3, P=0.005). Two (50%), 1 (20%), and 3 (38%) had non-SVT (all P=NS). 4 (100%), 2 (40%), and 2 (25%) had clinical heart failure (group 1&gt;2, P=0.019, group 1&gt;3, P&lt;0.001). Finally, 4 (100% and 80%) and 6 (75%) had RV enlargement on TTE (all P=NS). On 4D CT, 4 (100%), 5 (100%), and 5 (63%) of patients in groups 1, 2 and 3, showed RV enlargement (all P=NS); 4 (100%), 2 (40%), and 1 (13%) showed reduced RV motion (group 1&gt;2, P=0.019, group 1&gt;3, P&lt;0.001); 75, 100, and 0%, had RV fat invasion (group 1&gt;3, P=0.002, group 2&gt;3, P&lt;0.001); and 25, 0, and 0% showed bulging (all P=NS). Conclusions: Most patients had RV enlargement on TTE and/or 4D CT. Presence of epsilon waves, reduced RV motion, and RV fat invasion on 4D CT may differentiate groups 1 and 2 from group 3, inverted T waves in V1-3 leads or beyond may differentiate group 1 from group 3, SVT may differentiate group 2 from group 3 but only clinical heart failure may differentiate groups 1 and 2.

QRS dispersion using 252-leads Body Surface Mapping (BSM) – an explorative study of a novel diagnostic tool for Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

Abstract Background The diagnosis of ARVC is complex and challenging requiring multiple investigational tools, most of which include the demonstration of depolarization/conduction abnormalities, described in recent HRS consensus documents 2019. A simple and user friendly diagnostic tool is warranted. Purpose The purpose of our study was therefore to explore whether the analysis of QRS dispersion obtained from 252-leads recorded by a Body Surface Mapping (BSM) system can be used to identify ARVC patients as compared to the traditional ECG criteria including QRS dispersion measured by conventional 12 lead surface ECG. Methods 12 definite ARVC patients (10/12 with known pathogenic mutation) (Group 1) and 8 healthy family members tested negative for the family mutation served as controls (Group 0), were included. All patients underwent 12-lead ECG (50mm/sec), Signal-averaged ECG for late potentials and 252 lead BSM recordings. The QRS duration was measured in each of the 12 ECG leads manually with digital caliper. The QRS duration from the BSM leads were manually analyzed in Matlab by two observers unaware of the diagnosis. For each lead, the mean value of three randomly chosen beats was calculated. The QRS dispersion was calculated as the difference between the minimum and maximum value for both the 12 lead ECG and the BSM recordings. Results The mean age was 49,6 and 38,8 years in ARVC patients and controls, respectively. The number of males in the two groups were 8/12 and 5/8, respectively. Epsilon waves and Terminal Activation Duration (TAD) &amp;gt;55msec were detected in 6/12 and 8/12 ARVC patients, respectively, but in no controls. Late potentials were detected in 11/12 ARVC patients and in 2 controls. The QRS duration and QTc duration was not statistically different in the two Groups. The ECG-QRS dispersion was significantly more pronounced in Group 1 (42 ms ± 15, range 20–70 ms) than in Group 0 (26 ms ± 8, range 16–36 ms) (p=0.013). The BSM-QRS dispersion was significantly longer in Group 1 (68 ms ± 17, range 29–90ms) than in Group 0 (30 ms ± 7, range 22–41ms) (p=0.001). Only one ARVC patient had a BSM-QRS dispersion &amp;lt;50 msec, whereas none of the controls had a QRS dispersion over 50 msec (Fig. 1). Conclusion BSM-QRS dispersion, specifically using the cut off &amp;lt;50 ms, can potentially be a more sensitive and specific method than other ECG related techniques for diagnosing ARVC patients versus non-ARVC patients. Larger patient cohorts and further studies are required to confirm our findings. Figure 1. ECG and BSM-QRS dispersion Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Selanders Stiftelse

Clinical Presentation, Cardiac Magnetic Resonance Findings, and Prognosis of Patients with Arrhythmogenic Right Ventricular Cardiomyopathy - An Experience from Pakistan.

Objectives:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart-muscle disease, characterized by fibro-fatty replacement and ventricular arrhythmias, that primarily affects the right ventricle (RV). We aimed to look at the clinical presentation, cardiac magnetic resonance (CMR) imaging findings and prognosis of patients with ARVC in Pakistan.Material and Methods:It is a retrospective observational study, 17 consecutive patients with CMR and other findings consistent with ARVC, were enrolled from 2010 to 2019 at a single center.Results:Out of 17 patients, 12 (70.6%) were male with a mean age of 33.5 ± 17.5 years. Family history of sudden cardiac death was present in 3 (17.7%) patients while one (5.9%) patient had family history of ARVC. Syncope was the first presenting symptom in eight (47.1%) patients. On 12 leads ECG, T wave inversion in precordial leads was found in 6 (35.4%) patients, and epsilon wave was present in only 3 (17.7%) patients. On echocardiogram, 13 (76.5%) patients had dilated RV with reduced systolic function. On CMR, majority of patients (n = 14, 82.4%) were found to have RV dilatation with regional dyskinesia and fatty infiltration, 9 (52.9%) of them had left ventricular involvement also. Follow-up was available for 14 patients (82.4%) with a mean follow-up period of 35.5 ± 19.7 months. Three (21.4%) of them died and 10 (71.4%) got admissions for heart failure during follow-up period.Conclusion:Arrhythmia related events are the main presenting symptoms of ARVC in this region, and left ventricular involvement in ARVC is not rare in this population. The mortality is relatively high, probably due to advanced disease at the time of presentation and less medical facilities available.

P1733 Late onset of arrhytmogenic cardiomyopathy, unmasked by myocarditis - when multimodality imaging solves the puzzle

Abstract Introduction Arrhythmogenic cardiomyopathy (AC) is a genetic disease, associated with arrhythmic sudden death in young people. Since inflammation might be also present, differential diagnosis with myocarditis is necessary. We present a challenging case, initially diagnosed with ventricular tachycardia (VT) and acute myocardial infarction (AMI), in which multimodality imaging changed the initial diagnosis. Clinical case. A 68-year old woman with dyslipidaemia and hypertension was admitted with chest pain, negative T waves in anterior leads, epsilon wave in V1, V2 (Fig. A, B), negative troponin I (TpI), and elevated NT-proBNP (342 ng/ml). One month before, she was hospitalized for a monomorphic VT with left bundle branch block (LBBB) pattern, with hemodynamic instability, cardioverted electrically to sinus rhythm. Increased TpI suggested an AMI. She recalls an episode of flu with high fever (39°C) before admission. At current admission, transthoracic echo (TTE) revealed LVEF 52%, severe lateral wall hypokinesia, severe RV dysfunction with fractional area change 23%, and TAPSE 15 mm. Coronary angiography excluded significant lesions. Speckle tracking echo(STE) revealed patchy areas of decreased LV myocardial deformation (Fig. C), and decreased basal deformation in RV free wall(Fig. D). Cardiac magnetic resonance (CMR) revealed LVEF 59%, lateral and septal wall hypokinesia, late gadolinium enhancement (LGE) in mid-ventricular lateral wall and interventricular septum (Fig. F), with correspondent increased extracellular volume (ECV) &amp;gt;30%, increased native T1 time, increased T2 mapping, and small pericardial effusion (7 mm); RV was dilated (diastolic volume 107 ml/m2 and systolic volume 69 ml/m2), with severely decreased RV ejection fraction (RVEF) of 35%, hypokinesia of free wall, dyssynchronous contractions, and microaneurysms (Fig. E, F). Diagnosis was concluded for AC with delayed onset, revealed by an acute myocarditis. Betablocker, ACEI, and implantable cardioverter defibrillator (ICD) in secondary prevention were decided. Relatives were screened for the presence of AC. Patient`s daughter presented 8000 isolated monomorphic ventricular ectopic heart beats with LV origin, no echo signs, but incipient signs of AC on CMR (increased ECV on T1 mapping in 7 LV myocardial segments, without LGE). Discussion We presented a rare case of late arrhythmic onset of AC in a patient, in which the first aetiology of VT was considered to be ischaemic. VT with LBBB morphology can be caused by myocarditis, AMI, or AC. Similarly, epsilon wave with negative T waves in precordial leads may have multiple aetiologies. In our case, multimodality imaging approach excluded AMI and suggested an inflammatory cause for VT. CMR allowed the identification of morphologic condition AC and the trigger condition of myocarditis. Conclusions Our case highlights the importance of a multimodality imaging approach in diagnosing AC and myocarditis, for a correct and complete management. Abstract P1733 Figure.

P1804 Phenotypic overlap between Brugada syndrome and arrhythmogenic cardiomyopathy

Abstract Background Brugada syndrome (BrS) and arrhythmogenic cardiomyopathy (AC) are genetic cardiac diseases characterized by high risk for sudden cardiac death. Although BrS and AC are different clinical entities, experimental research and clinical cases suggest a phenotypic overlap. Purpose We aimed to assess the prevalence of structural and electrical AC diagnostic criteria in BrS patients. Methods In this multicentre study we acquired electrocardiograms (ECG) and transthoracic echocardiography in BrS patients between May and September 2018. We assessed the right ventricular outflow tract (RVOT) diameter, fractional area change (FAC) from echocardiography, and depolarization and repolarization criteria from ECG using parameter cut offs and definitions according to 2010 AC Task Force criteria. Results We included 123 BrS patients [54 (40-62) years old, 63 (51%) women]. Although, by definition, no akinesia, dyskinesia or aneurisms were present, 61 (50%) BrS patients had major criteria for dilated RVOT and/or reduced FAC, and 39 (32%) had at least one minor RVOT or FAC criterion (Figure). ECG showed minor repolarization and/or depolarization criteria in 30 (24%) BrS patients. No epsilon waves or major T-wave inversions were observed. Conclusion Half of BrS patients had evident major RVOT dilation and/or reduced FAC and one quarter had minor electrical features of AC. These findings suggest a significant phenotypical continuum between BrS and AC. Abstract P1804 Figure.

Diagnostic value of additional right precordial leads both at rest and at peak stress test in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (ARVC/D) patients

ECG late depolarization abnormality called epsilon wave (ɛ) is a major diagnostic criterion in ARVC/D patients according to Task Force. As ARVC/D induces progressive right ventricular enlargement, whether or not additional right precordial leads (X1, X2, V3R, V4R) may increase ECG diagnostic sensitivity at rest and/or during exercise has never been systematically investigated. We studied 3 groups (G) of subjects. G1: 17 propositus patients with desmosomal mutation; G2: 17 first degree relative gene carriers; G3: 20 controls. All subjects were paired between groups for age, BSA, sex and sport practice. A 16 leads ECG including additional right precordial leads X1, X2, V3R, V4R was performed in each case both at rest and at peak stress. Recordings were amplified up to 100 mm/s and 40 mm/mV and retrospectively analyzed by two investigators blinded to patient status. All subjects reached a sustained power of similar strength (160 ± 50 W) on cycloergometer. At rest, by including standard (V1, V2) and additional right precordial leads, an ɛ was shown in 14/34 patients (41%, 7 in G1, 7 in G2). Among them 4 (12%, 2 in G1, 2 in G2) showed an ɛ exclusively in at least one additional lead. At peak stress, an ɛ was noticed in 19/34 patients (56%, 12 in G1, 7 in G2). Among them, 9 patients (26%, 7 in G1, 2 in G2) showed an ɛ exclusively in at least one additional lead. In other words, in 5/34 patients (15%, all in G1) not showing any ɛ at rest, peak stress unmasked a new ɛ, exclusively in at least one additional right precordial lead. No ɛ was detected in G3, neither at rest nor at stress. By combining rest and stress test ECG, the use of additional right precordial leads X1, X2, V3R, V4R, enhances by 27% the detection of ɛ waves (major criterion), more often in propositus than in relatives, as compared to usual precordial derivations alone, and should be proposed for inclusion among ARVC/D Task Force criteria.

Late Presentation of Arrhythmogenic Right Ventricular Cardiomyopathy : Role of Non Invasive Modalities for The Diagnosis

Background : Arrhythmogenic right ventricular cardiomyopathy(ARVC) is an inherited myocardial disease affecting predominantly young people and manifests as sustained ventricular tachycardia, sudden cardiac death (SCD) or heart failure. However, its first manifestation in older patients is infrequent. Diagnosis of ARVC remains a clinical challenge and need further investigation. Our case report investigated role of non invasive modalities for diagnosis of ARVC patient.&#x0D; Case Presentation : A 65 year old man was admitted to the hospital with symptoms of palpitationand near syncope. An Electrocardiogram (ECG) showed a sustained VT with LBBB morphology and inferior axis. The patient was cardioverted to sinus rhytm with a single 100J shock. Postcardioversion ECG showed an epsilon wave in right precordial leads. Echocardiography revealed extensive RV enlargement and reduce function. Our patient had three major (RV aneurysm, epsilon wave and T wave inversion) and one minor criteria (sustained LBBB type-VT with inferior axis)making the diagnosis of ARVC definite according to the revised Task Forced Criteria.&#x0D; Conclusion: ARVC may have a very late presentation and this diagnosis should be considered as a potential cause of sustained VT of RV origin among the elderly. ECG and echocardiography as non invasive modalities have an important role for the diagnosis of patients with suspected ARVC.&#x0D; Keywords :Arrhythmogenic right ventricular cardiomyopathy,ventricular tachycardia, sudden cardiac death, diagnosis.

Predictors of Adverse Outcomes in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy: A Meta-Analysis of Observational Studies.

Arrhythmogenic cardiomyopathy (AC) is a hereditary disorder characterized by degeneration of cardiac myocytes and their subsequent replacement by fat and fibrous tissue primarily in the right ventricle. Our study aimed to systematically evaluate the impact of significant demographic, clinical, electrocardiographic, and echocardiographic factors in arrhythmic events in AC patients. MEDLINE and Cochrane library databases were manually searched without year or language restriction or any other limits until July 31, 2017. A pooled odds ratio with 95% confidence intervals was calculated for each of the risk factors. Our search retrieved 26 studies (n = 2680 patients, mean age: 37.9 years old, males: 51.9%) which were included in the quantitative synthesis. The most reliable predicting factors/parameters are the following: (1) male gender, (2) presyncope, (3) left ventricular dysfunction, (4) T-wave inversions in inferior leads, (5) proband status, (6) late potentials, (7) syncope, (8) inducibility at electrophysiological study, (9) right ventricular dysfunction, (10) epsilon waves, and (11) premature ventricular contractions greater than 1000/24 h. On the contrary, family history of sudden cardiac death, palpitations, premature ventricular contractions greater than 500/24 h, and T-wave inversions in right precordial leads fail to determine the outcome in this meta-analysis. In conclusion, multiple risk factors have been associated with arrhythmic events in AC patients. However, larger studies are needed to discriminate those patients who will benefit from implantable cardioverter defibrillators.

High risk of heart failure associated with desmoglein-2 mutations compared to plakophilin-2 mutations in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

Previous studies suggested that genetic status affects the clinical course of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients. The aim of this study was to compare the outcome of desmoglein-2 (DSG2) mutation carriers to those who carry the plakophilin-2 (PKP2) mutation, the most common ARVC/D-associated gene. Consecutive ARVC/D patients carrying a pathogenic mutation in PKP2 or DSG2 were selected from a national ARVC/D registry. The cumulative freedom from sustained ventricular arrhythmia and cardiac transplantation/death from heart failure (HF) during follow-up was assessed, compared between PKP2 and DSG2, and predictors for ventricular arrhythmia and HF events determined. Overall, 118 patients from 78 families were included: 27 (23%) carried a DSG2 mutation and 91 (77%) a PKP2 mutation. There were no significant differences between DSG2 and PKP2 mutation carriers concerning gender, proband status, age at diagnosis, T-wave inversion, or right ventricular dysfunction at baseline. DSG2 patients displayed more frequent epsilon wave (37% vs. 17%, P = 0.048) and left ventricular dysfunction at diagnosis (54% vs. 10%, P < 0.001). During a median follow-up of 5.6 years (2.5-16), DSG2 and PKP2 mutation carriers displayed a similar risk of sustained ventricular arrhythmia (log-rank P = 0.20), but DSG2 mutation carriers were at higher risk of transplantation/HF-related death (log-rank P < 0.001). The presence of a DSG2 mutation vs. PKP2 mutation was a predictor of transplantation/HF-related death in univariate Cox analysis (P = 0.0005). In this multicentre cohort, DSG2 mutation carriers were found to be at high risk of end-stage HF compared to PKP2 mutation carriers, supporting careful haemodynamic monitoring of these patients. The benefit of early HF treatment needs to be assessed in DSG2 carriers.

Clinical features and arrhythmic complications of patients with pediatric-onset arrhythmogenic right ventricular dysplasia.

Objective:Arrhythmogenic right ventricular dysplasia (ARVD) is a myocardial genetic disease that occurs primarily in the right ventricle. Patients with ARVD may present with severe ventricular arrhythmias, syncope, and cardiac arrest. The purpose of this study is to evaluate the clinical features and arrhythmic complications of patients with pediatric-onset ARVD.Methods:Patients diagnosed with ARVD between January 2010 and January 2019 were included in this study.Results:A total of 19 patients with ARVD were evaluated. Of them, 15 patients were male, and their mean age was 12±4 years. The most common symptoms were palpitations (n=6), syncope (n=4), and heart failure symptoms (n=2). Five patients were asymptomatic. Thirteen patients had an epsilon wave; all patients ≥14 years had a T wave inversion in V1–3. Premature ventricular contractions (PVCs) were observed in 15 patients, and ventricular tachycardia (VT) was observed in 9 patients. All patients underwent cardiac magnetic resonance imaging (MRI). Echocardiography and cardiac MRI of two patients were normal at the time of admission; patients were in the concealed phase, and the diagnosis was made by ECG, Holter monitoring, and genetic findings. We administered a beta-blocker in all patients. Two patients underwent an electrophysiological study and ablation because of PVC/VT. An implantable cardiac defibrillator was implanted in 8 patients. The mean follow-up period was 21.5±11 months. Two patients were deceased with incessant VT and heart failure, and one patient was deceased with multiorgan dysfunction after biventricular assist device implantation (n=3).Conclusion:Diagnosis of pediatric-onset ARVD might be much more difficult in children. Sudden cardiac death might be prevented in the early period by raising the awareness of physicians about the disorder. Prevention of sudden death with implantable cardiac defibrillators is crucial in the management of these patients. It should be kept in mind that children with structurally normal hearts may present with an earlier concealed phase and can be diagnosed with ARVD.

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.

Indications for loop recorder implantation for syncope

Implantable loop recorder with discontinuous ECG recording enables monitoring of heart rhythm over several years. Consequently, in patients with recurrent syncope it is possible to record an ECG during the next syncopal event to obtain symptom-ECG correlations. In patients with recurrent syncope of unknown origin, the implantation of aloop recorder leads to an earlier diagnosis and an asystole is more often detected as the cause of the recurrent syncope. In addition, the loop recorder identifies patients who will benefit from pacemaker implantation. An established indication for early implantation of aloop recorder is given in patients with recurrent syncope and no high-risk marker, e. g., reduced left ventricular function, valve disease, history of myocardial infarction or ECG findings such as bifascicular block, pre-excitation, long QT syndrome or an epsilon wave. These patients should receive acomplete cardiological work-up with the aim of detecting the underlying heart disease. Patients with no conclusive findings should also receive aloop recorder. Arelative indication is given for patients with recurrent syncope and injuries in order to predict the effect of pacemaker implantation. Possible indication is given for patients with transient loss of consciousness to rule out an arrhythmogenic origin.

Epsilon wave back in force

Four decades of progress in understanding the electrogenesis, clinical value and recording methods of the epsilon wave have been achieved since it was first recognized in 1977. According to the new 2010 Task Force criteria, epsilon waves are a major criterion in the diagnosis of arrhythmogenic right ventricular dysplasia. Epsilon waves can be observed in the right precordial leads when a relevant intramyocardial conduction defect is present in the right ventricle. In this paper, we summarize the progress, challenge, and controversies in the definition of epsilon waves.