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The early repolarization pattern (ERp) is an electrocardiographic finding previously associated with arrhythmic risk in adults. The purpose of this study is to evaluate the prevalence and characteristics of ERp in a group of adolescent athletes according to gender. Furthermore, potential associations with clinical, electrocardiographic, and echocardiographic parameters are explored.In this cross-sectional study young athletes (age 18 years) were consecutively enrolled during the annual pre-participation evaluation, undergoing also transthoracic echocardiography assessment from January 2015 to March 2020.The prevalence of ERp was 27% in the whole population. Athletes with ERp were more frequently men practicing endurance sports. Women with ERp showed lower heart rate at rest, greater posterior, and relative ventricular wall thickness than those without ERp. Men with ERp presented higher systolic blood pressure at peak exercise, greater septal wall thickness, and indexed left ventricular mass than those without ERp. Both genders with ERp showed increased QRS voltage and narrower QRS duration. The ERp phenotype in men was more frequently notched with higher amplitude and ascending ST segment. Women's ERp presented more frequently a slurred morphology, especially in the inferior leads, and horizontal ST slope. No differences emerged in the occurrence of arrhythmias at rest and during maximal exercise test between groups, even considering higher risk phenotypes.ERp is an ECG finding compatible with normal cardiac adaptations to training in young athletes. ERp demonstrated gender differences regarding phenotypes previously associated with increased cardiovascular risk, not showing any differences in arrhythmias during maximal exercise test.

In the wide phenotypic spectrum of cardiomyopathies, sudden cardiac death (SCD) has always been the most visible and devastating disease complication. The introduction of implantable cardioverter-defibrillators for SCD prevention by the late 1980s has moved the question from how to whom we should protect from SCD, leaving clinicians with a measure of uncertainty regarding the most reliable option to guide identification of the highest-risk patients. In this review, we will go through all the available evidence in the field of arrhythmic expression and arrhythmic risk stratification in the different phenotypes of cardiomyopathies to provide practical suggestions in daily clinical management.

Cardiac magnetic resonance imaging (CMR) is a non-invasive, multiplanar, and high spatial resolution imaging technique, which represents the current gold standard for the evaluation of biventricular volumes and function. Furthermore, unlike other methods, it has the great advantage of characterizing the myocardial tissue by identifying the presence of alterations, such as oedema and focal and diffuse fibrosis. In particular, the late gadolinium enhancement technique makes it possible to identify areas of focal fibrosis that often constitute the substrate for the triggering of threatening ventricular arrhythmias at the basis of sudden cardiac death. For this reason, the use of CMR in the study of cardiomyopathies has become of primary importance, both for the differential diagnosis and for patient risk stratification. In this brief review, the ability of CMR in prognostic stratification of patients with dilated, hypertrophic, and arrhythmogenic cardiomyopathy will be analysed. In particular, the role of CMR in the prediction of arrhythmic risk and in the decision-making process for the implantation of a cardiac defibrillator will be examined.

Hypertensive left ventricular hypertrophy (HTN LVH) is associated with almost threefold increased risk of ventricular tachycardia (VT)/ventricular fibrillation (VF). Furthermore, HTN LVH increases the risk of sudden cardiac death (SCD). The reverse LV remodeling due to efficient antihypertensive therapy lowers the incidence rates of cardiovascular events and SCD and the vast majority of available arterial hypertension (HTN) guidelines recommend renin angiotensin system (RAS) blockers and calcium channel blockers (CCBs) for HTN LVH aiming for LVH regression. On the other hand, beta blockers (BBs) as a class are not recommended in HTN LVH due to their insufficient capacity to reverse LVH remodeling even though they are recommended as the first-line drugs for prevention/treatment of VT/VF (in general, unrelated to HTN LVH). Moreover, BBs are the best antiarrhythmic (against VT/VF) among antihypertensive drugs. Despite that, BBs are currently not recommended for LVH treatment in HTN Guidelines. It is important to prevent VT/VF in patients at high risk, such as those with HTN LVH. Therefore, certain BBs (such as Bisoprolol) may be reevaluated in guidelines for HTN (in the section of HTN LVH).

A 45-year-old male, hypertensive and obese presented with a 3-months history of short episodes of intermittent palpitations. Clinical examination was unremarkable; however, the electrocardiogram documented major right bundle branch block and the presence of fragmented QRS in all precordial leads. His echocardiography documented a dilated left ventricle, with mild systolic dysfunction and moderate biventricular reduction of the global longitudinal strain. On angiography, the epicardial coronary arteries were normal. A cardiac MRI revealed diffuse transmural fi brotic lesions with non ischemic pattern of the ventricles, suggestive of chronic myocarditis. The electrophysiological study induced two ventricular tachycardia morphologies which were ablated and an ICD for sudden cardiac death primary prevention was implanted. Fortunately, at 6 months follow-up our patient had no ICD therapies and reported an alleviation of symptoms.

ECG is a common diagnostic tool in medical practice. Sudden cardiac death (SCD) is a rare but devastating event. The most common cause of SCD in the young is a primary arrhythmic event, which is often produced by malignant ventricular arrhythmia. Several electrocardiographic markers for ventricular repolarization and depolarization have been proposed to predict this arrhythmic risk and SCD in children. Although many of these parameters can easily be used in clinical practice, some of them need specific techniques for interpretation. In this review, we summarized the current knowledge regarding the clinical importance and the ability of these ECG parameters to predict adverse cardiac events in the pediatric population.

Coronavirus disease of 2019 (COVID-19) is a cause of significant morbidity and mortality worldwide. Although COVID-19 clinical manifestations are mainly respiratory, major cardiac complications are being reported. The mechanism of cardiac injury and arrhythmias is unclear. Also, drugs currently used to treat the COVID-19 may prolong the QT interval and may have a proarrhythmic propensity. The study aims to investigate the effects of COVID-19 infection with asymptomatic and mild symptoms on trans-myocardial repolarization parameters in children without treatment. A total of 105 COVID-19 patients were compared with 40 healthy children. The patient and control group data were compared by calculating the QT interval, corrected QT (QTc), QT dispersion (QTd), QTc dispersion (QTcd), Tp-e, Tp-e dispersion, Tp-e/QT ratio, and Tp-e/QTc ratio on the 12-lead surface electrocardiogram. The mean age was determined as 11.2 ± 0.3 years in the patient group, and 10.8 ± 2.1 years in the control group. In the COVID-19 group, QTd, QTcd, Tp-e, Tp-e dispersion, Tp-e/QT ratio and Tp-e/QTc ratio were statistically higher than the control group. The ventricular repolarization was impaired even in asymptomatic children with COVID-19 infection. These results suggest the need to further assess the long terms risks of prolonged QT dispersion in the setting of COVID-19 infection.

High-level exercise has been associated with a malignant phenotype in desmosomal and genotype-negative forms of arrhythmogenic right ventricular cardiomyopathy (ARVC). This is the first study to examine this issue with ARVC secondary to the TMEM43 p.S358L mutation.The purpose of this study was to evaluate the impact of exercise on arrhythmic risk and cardiac death in TMEM43 p.S358L ARVC.Individuals with the TMEM43 p.S358L mutation enrolled in a prospective registry who had received a primary prevention implantable cardioverter-defibrillator (ICD) were invited to complete the modified Paffenbarger Physical Activity Questionnaire to assess their physical activity in the year before their ICD implantation. Time-to-event analyses using unadjusted and adjusted Cox proportional hazards models evaluated associations between physical activity and first appropriate ICD discharge secondary to malignant ventricular arrhythmia or cardiac death.In 80 subjects with the TMEM43 p.S358L mutation, exercise ≥9.0 metabolic equivalent of task (MET)-hours/day (high level) in the year before ICD implantation was associated with an adjusted 9.1-fold increased hazard of first appropriate ICD discharge (there were no deaths) relative to physical activity9.0 MET-hours/day (moderate level) (95% confidence interval [CI] 3.3-24.6 MET-hours/day; P.001). The median age from birth to first appropriate ICD discharge was 58.5 years (95% CI 56.5-60.5 years) vs 35.8 years (95% CI 28.2-43.4 years) (P.001) in subjects in moderate- and high-level exercise groups, respectively.Exercise ≥9.0 MET-hours/day is associated with an increased risk of malignant ventricular arrhythmias in the TMEM43 p.S358L subtype of ARVC. Extrapolating these data, we suggest molecular testing be offered in early childhood to inform exercise choices reflective of the genotype.

In a 37-year-old cardiac arrest survivor with autosomal dominant Carvajal syndrome and arrhythmogenic cardiomyopathy, a desmoplakin mutation was identified. Cascade screening identified 2 affected family members and 2 healthy children carrying the mutation. Strategies for primary and secondary risk prevention emphasize the role of genetic testing in rare cardiomyopathies. (Level of Difficulty: Advanced.), Graphical abstract, In a 37-year-old cardiac arrest survivor with autosomal dominant Carvajal syndrome and arrhythmogenic cardiomyopathy, a desmoplakin mutation was…

Background: Arrhythmogenic cardiomyopathy (AC) is a life-threatening disease which predispose to malignant arrhythmias and sudden cardiac death (SCD) in the early stages of the disease. Risk stratification relies on the electrical, genetic, and imaging data. Our study aimed to investigate how myocardial deformation parameters may identify the subjects at risk of known predictors of major ventricular arrhythmias.Methods: A cohort of 45 subjects with definite or borderline diagnosis of AC was characterized using the advanced transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) and divided into the groups according to the potential arrhythmic risk markers, such as non-sustained ventricular tachycardia (NSVT), late gadolinium enhancement (LGE), and genetic status. Layer-specific global longitudinal strain (GLS) by TTE 2D speckle tracking was compared in patients with and without these arrhythmic risk markers.Results: In this study, 23 (51.1%) patients were men with mean age of 43 ± 16 years. Next-generation sequencing identified a potential pathogenic mutation in 39 (86.7%) patients. Thirty-nine patients presented LGE (73.3%), mostly located at the subepicardial-to-mesocardial layers. A layer-specific-GLS analysis showed worse GLS values at the epicardial and mesocardial layers in the subjects with NSVT and LGE. The epicardial GLS values of −15.4 and −16.1% were the best cut-off values for identifying the individuals with NSVT and LGE, respectively, regardless of left ventricular ejection fraction (LVEF).Conclusions: The layer-specific GLS assessment identified the subjects with high-risk arrhythmic features in AC, such as NSVT and LGE. An epicardial GLS may emerge as a potential instrument for detecting the subjects at risk of SCD in AC.

Background Arrhythmic risk of patients with left ventricular arrhythmogenic cardiomyopathy (LVAC) is unpredictable. Purpose To identify risk facors associated with major ventricular tachyarrhythmias (VTA) in clinically-suspected LVAC patients. Methods We enrolled 127 consecutive patients (69% males, age 46±13 y, LVEF 54±7%) with clinically-suspected LVAC. All patients presented with either major (VT, VF) or minor VTA (NSVT, frequent VEB), and underwent extensive diagnostic workup to rule-out alternative diagnoses. Medical treatment and ICD implant were clinically-driven. Prospective follow-up was obtained via sequential 24h-Holter ECG (2–4/y) with or without continuous arrhythmia monitoring (ICD or implantable loop recorders, ILR). The primary endpoint was occurrence of major VTA (VT/VF/ICD therapy) by 24-month follow-up. Results At presentation, 56 (44%) and 71 patients (56%) had, respectively, major and minor VTA. Variants in desmosomal genes were identified in 7 of the 9 patients with clinically-indicated genetic test. Delayed gadolinium enhancement (DGE, average 23±12% of the LV mass) had anteroseptal distribution in 43 cases (34%). Monitoring strategy included ICD (n=64), ILR (n=33), or sequential Holer ECGs (n=30). By 24-month follow-up, major VTA occurred in 32 patients (25%). At univariable anlysis, major VTA onset (HR 16.8, 95% CI 5.4–52.2, p Conclusion Our preliminary experience suggests that, in patients with clinically-suspected LVAC, major VTA onset and anteroseptal DGE are relevant risk factors for major arrhythmic events by 24-month follow-up. Funding Acknowledgement Type of funding sources: None.

INTRODUCTION: Although atrial fibrillation is the most prevalent disorder of electrical conduction, the mechanisms behind atrial arrhythmias remain elusive. To address this challenge, we developed a robust in vitro model of 3D atrial microtissue from human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and evaluated chamber-specific chemical responses experimentally and computationally. METHODS: We differentiated atrial and ventricular cardiomyocytes (aCMs/vCMs) from GCaMP6f-expressing hiPSCs and assessed spontaneous AP activity using fluorescence imaging. Self-assembling 3D microtissues were formed with lactate purified CMs and 5% human cardiac fibroblasts and electrically stimulated for one week before high resolution action potential (AP) optical mapping. AP responses to the atrial-specific potassium repolarizing current I(Kur)-blocker 4-Aminopyridine (4-AP) and funny current I(f)-blocker Ivabradine were characterized within their therapeutic window. Finally, we expanded upon a published hiPSC-CM computational model by incorporating the atrial-specific I(Kur) current, modifying ion channel conductances to match the AP waveforms of our microtissues, and employing the updated model to reinforce our experimental findings. RESULTS: High purity CMs (> 75% cTnT(+)) demonstrated subtype specification by MLC2v expression. Spontaneous beating rates significantly decreased following 3D microtissue formation, with atrial microtissues characterized by their faster spontaneous beating rate, slower AP rise time, and shorter AP duration (APD) compared to ventricular microtissues. We measured atrial-specific responses, including dose-dependent APD prolongation with 4-AP treatment and dose-dependent reduction in spontaneous activity post-Ivabradine treatment. CONCLUSION: The presented in vitro platform for screening atrial-specific responses is both robust and sensitive, with high throughput, enabling studies focused at elucidating the mechanisms underlying atrial arrhythmias. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00703-x.

Aims This study aims to improve risk stratification for primary prevention implantable cardioverter defibrillator (ICD) implantation by developing a new mutation-specific prediction model for malignant ventricular arrhythmia (VA) in phospholamban (PLN) p.Arg14del mutation carriers. The proposed model is compared to an existing PLN risk model. Methods and results Data were collected from PLN p.Arg14del mutation carriers with no history of malignant VA at baseline, identified between 2009 and 2020. Malignant VA was defined as sustained VA, appropriate ICD intervention, or (aborted) sudden cardiac death. A prediction model was developed using Cox regression. The study cohort consisted of 679 PLN p.Arg14del mutation carriers, with a minority of index patients (17%) and male sex (43%), and a median age of 42 years [interquartile range (IQR) 27–55]. During a median follow-up of 4.3 years (IQR 1.7–7.4), 72 (10.6%) carriers experienced malignant VA. Significant predictors were left ventricular ejection fraction, premature ventricular contraction count/24 h, amount of negative T waves, and presence of low-voltage electrocardiogram. The multivariable model had an excellent discriminative ability {C-statistic 0.83 [95% confidence interval (CI) 0.78–0.88]}. Applying the existing PLN risk model to the complete cohort yielded a C-statistic of 0.68 (95% CI 0.61–0.75). Conclusion This new mutation-specific prediction model for individual VA risk in PLN p.Arg14del mutation carriers is superior to the existing PLN risk model, suggesting that risk prediction using mutation-specific phenotypic features can improve accuracy compared to a more generic approach., Graphical Abstract Malignant VA risk prediction in PLN p.Arg14del carriers. With the mutation specific risk factors low and high risk groups can be identified. PLN, Phospholamban; VA, Ventricular arrhythmia.

Objectives This study sought to evaluate the potential clinical impact of using 3-dimensional echocardiography (3DE) to measure left ventricular ejection fraction (LVEF) in patients considered for implantable cardioverter-defibrillator (ICD) implantation and to assess the predictive value of 3DE LVEF for arrhythmic events. Background ICD therapy is currently recommended to prevent sudden cardiac death in patients with symptomatic heart failure and LVEF ≤35%, and in asymptomatic patients with ischemic heart disease and LVEF ≤30%. Two-dimensional echocardiography (2DE) is currently used to calculate LVEF. However, 3DE has been reported to be more reproducible and accurate than 2DE to measure LVEF. Methods The study prospectively enrolled 172 patients with LV dysfunction (71% ischemic). Both 2DE and 3DE LVEF were obtained during the same study. The outcome was the occurrence of major arrhythmic events (sudden cardiac death, aborted cardiac arrest, appropriate ICD therapy). Results After a median follow up of 56 (range 18 to 65) months, major arrhythmic events occurred in 30% of the patients. Compared with 2DE, 3DE changed the assignment above or below the LVEF thresholds for ICD implantation in 20% of patients, most of them having 2DE LVEFs within ± 10% from threshold. By cause-specific hazard model, 3DE LVEF was the only independent predictor of the occurrence of major arrhythmic events. Conclusions LVEF by 3DE was an independent predictor of major arrhythmic events and improved arrhythmic risk prediction in patients with LV dysfunction. When compared with 2DE LVEF, 3DE measurement of LVEF may change the decision to implant an ICD in a sizable number of patients.

Background Survivors of myocardial infarction are at increased risk of late ventricular arrhythmias, with infarct size and scar heterogeneity being key determinants of arrhythmic risk. Gap junctions facilitate the passage of small ions and morphogenic cell signaling between myocytes. We hypothesized that gap junctions enhancement during infarction–reperfusion modulates structural and electrophysiological remodeling and reduces late arrhythmogenesis. Methods and Results Infarction–reperfusion surgery was carried out in male Sprague‐Dawley rats followed by 7 days of rotigaptide or saline administration. The in vivo and ex vivo arrhythmogenicity was characterized by programmed electrical stimulation 3 weeks later, followed by diffusion‐weighted magnetic resonance imaging and Masson's trichrome histology. Three weeks after 7‐day postinfarction administration of rotigaptide, ventricular tachycardia/ventricular fibrillation was induced on programmed electrical stimulation in 20% and 53% of rats, respectively (rotigaptide versus control), resulting in reduction of arrhythmia score (3.2 versus 1.4, P =0.018), associated with the reduced magnetic resonance imaging parameters fractional anisotropy (fractional anisotropy: −5% versus −15%; P =0.062) and mean diffusivity (mean diffusivity: 2% versus 6%, P =0.042), and remodeling of the 3‐dimensional laminar structure of the infarct border zone with reduction of the mean (16° versus 19°, P =0.013) and the dispersion (9° versus 12°, P =0.015) of the myofiber transverse angle. There was no change in ECG features, spontaneous arrhythmias, or mortality. Conclusions Enhancement of gap junctions function by rotigaptide administered during the early healing phase in reperfused infarction reduces later complexity of infarct scar morphology and programmed electrical stimulation–induced arrhythmias, and merits further exploration as a feasible and practicable intervention in the acute myocardial infarction management to reduce late arrhythmic risk.

The prediction and prevention of sudden cardiac death is the philosopher’s stone of clinical cardiac electrophysiology. Sports can act as triggers of fatal arrhythmias and therefore it is essential to promptly frame the athlete at risk and to carefully evaluate the suitability for both competitive and recreational sports activity. A history of syncope or palpitations, the presence of premature ventricular complexes or more complex arrhythmias, a reduced left ventricular systolic function, or the presence of known or familiar heart disease should prompt a thorough evaluation with second level examinations. In this regard, cardiac magnetic resonance and electrophysiological study play important roles in the diagnostic work-up. The role of genetics is increasing both in cardiomyopathies and in channelopathies, and a careful evaluation must be focused on genotype positive/phenotype negative subjects. In addition to being a trigger for fatal arrhythmias in certain cardiomyopathies, sports also play a role in the progression of the disease itself, especially in the case arrhythmogenic right ventricular cardiomyopathy. In this paper, we review the latest European guidelines on sport cardiology in patients with cardiovascular diseases, focusing on arrhythmic risk stratification and the management of cardiomyopathies and channelopathies.

Incidence of cardiac arrhythmias increases significantly with age. In order to effectively stratify arrhythmic risk in the aging population it is crucial to elucidate the relevant underlying molecular mechanisms. The changes underlying age-related electrophysiological disruption appear to be closely associated with mitochondrial dysfunction. Thus, the present review examines the mechanisms by which age-related mitochondrial dysfunction promotes arrhythmic triggers and substrate. Namely, via alterations in plasmalemmal ionic currents (both sodium and potassium), gap junctions, cellular Ca2+homeostasis, and cardiac fibrosis. Stratification of patients' mitochondrial function status permits application of appropriate anti-arrhythmic therapies. Here, we discuss novel potential anti-arrhythmic pharmacological interventions that specifically target upstream mitochondrial function and hence ameliorates the need for therapies targeting downstream changes which have constituted traditional antiarrhythmic therapy.

Myocarditis is an inflammatory disease of cardiac muscle with a variable clinical presentation, ranging from asymptomatic cases to different degrees of left ventricular systolic dysfunction up to heart failure and dilated heart disease. Ventricular arrhythmias (VA) can occur in patients with myocarditis and implantable cardioverter defibrillator (ICD) may be indicated in patients with life-threatening VA who are not in the acute phase of myocarditis and who are receiving optimal medical therapy. Reduced left ventricular ejection fraction (LVEF) below 35%, which is used as the main criterion for stratifying the risk of sudden cardiac death (SCD), has low sensitivity and low specificity for arrhythmic risk stratification in patients with myocarditis. Myocardial scar is the main determinant for VA in these patients. Cardiac magnetic resonance imaging (CMR), using late gadolinium enhancement(LGE), has an excellent ability to determinate the extension and characterization of myocardial scar, indeed CMR can potentially improve SCD risk stratification and indication for ICD implantation in patients with myocarditis. We present a case of a 36 years-old male presenting to the Emergency Department with a monomorphic sustained ventricular tachycardia in whom MRI revealed myocardial-pericardial recurrent inflammatory involvement and worsening disease progression. ICD was implanted in consideration of the high risk of life-threatening arrhythmias.

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Area Network on Cardiovascular Diseases (ERA-CVD) Background Arrhythmogenic cardiomyopathy (AC) is an inheritable heart disease characterized by high risk of life-threatening ventricular arrhythmia. Male sex has been reported as a risk factor of high disease penetrance and arrhythmia, but data on sex-specific phenotype in AC are sparse. Purpose To assess sex-specific disease progression in AC patients and structural cardiac changes at time of arrhythmic event. Methods We included consecutive AC patients in a longitudinal cohort study. We performed echocardiography at baseline according to Task Force Criteria of 2010 with additional parameters including strain. Patients were followed with repeated echocardiographic examinations. Ventricular arrhythmia was defined as aborted cardiac arrest, sustained ventricular tachycardia or appropriate therapy by an implantable cardioverter-defibrillator. In patients with documented first time ventricular arrhythmias, echocardiographic findings obtained ±30 days around the event was noted separately. Results We included 191 AC patients (46% female, 51% probands, age 41 ± 17 years) of which 88% had ≥2 echocardiographic examinations during 6.9 (IQR 4.7-9.8) years of follow up. Females and males had similar progression rate of right ventricular dimensions and left ventricular function, but right ventricular function decreased more in females (Figure). Arrhythmic events occurred in 85 (45%) patients and 39 patients had an echocardiographic examination at the time of their first event. There was no difference in right ventricular diameters or right or left ventricular function between females and males at the time of first arrhythmic event (right ventricular outflow tract diameter: 35 ± 7 mm vs. 39 ± 7 mm, p = 0.16, right ventricular fractional area change: 34 ± 9 % vs. 29 ± 11 %, p = 0.26, left ventricular global longitudinal strain: -18.8 ± 3.0 % vs. 17.2 ± 2.2 %, p = 0.12, respectively). Conclusion Disease progression was similar in male and female AC patients indicating no accelerated disease progression in males. First arrhythmic event occurred at similar cardiac dysfunction and diameters in both sexes indicating no lower risk in females. Abstract Figure.

Background Cardiac sympathetic denervation (CSD) has been used as a bailout strategy for refractory ventricular tachycardia (VT). Risk of VT recurrence in patients with scar‐related monomorphic VT referred for CSD and the extent to which CSD can modify this risk is unknown. We aimed to quantify arrhythmia recurrence risk and impact of CSD in this population. Methods and Results Adjusted competing risk time to event models were developed to adjust for risk of VT recurrence and sustained VT/implantable cardioverter–defibrillator shocks after VT ablation based on patient comorbidities at the time of VT ablation. Adjusted VT and implantable cardioverter–defibrillator shock recurrence rates were estimated for the subgroup who subsequently required CSD after ablation. The expected adjusted recurrence rates were then compared with the observed rates after CSD. Data from 381 patients with scar‐mediated monomorphic VT who underwent VT ablation were analyzed, excluding patients with polymorphic VT. Sixty eight patients underwent CSD for recurrent VT. CSD reduced the expected adjusted VT recurrence rate by 36% (expected rate of 5.61 versus observed rate of 3.58 per 100 person‐months, P =0.01) and the sustained VT/implantable cardioverter–defibrillator shock rates by 34% (expected rate of 4.34 versus observed 2.85 per 100 person‐months, P =0.03). The median number of sustained VT/implantable cardioverter–defibrillator shocks in the year before versus the year after CSD was reduced by 90% (10 versus 1, P Conclusions Patients referred for CSD for refractory scar‐mediated monomorphic VT are at a higher risk of VT recurrence after ablation as compared with those not requiring CSD, mostly because of their cardiac comorbidities. CSD significantly reduced both the expected risk of recurrences and VT burden.

Long QT syndrome type 2 (LQT2) is an inherited disease leading to arrhythmias and sudden death often in response to an abrupt sympathetic stimulus. Heart period (HP) and QT interval variability analyses were carried out over asymptomatic (ASYMP, n=10, age 39.0±11.0 yrs, 9 males) and symptomatic (SYMP, n=7, age 41.7±12.8 yrs, 4 males) LQT2 patients. Beat-to-beat series were derived from 24h Holter ECG recordings during daytime and nighttime. In addition to HP and QT mean and variance, we calculated HP power in high frequency (HF, from 0.15 to 0.5 Hz) band as a marker of vagal modulation directed to sinus node and QT power in low frequency (LF, from 0.04 to 0.15 Hz) band as a marker of sympathetic modulation directed to ventricles. HP and QT means exhibited significant day-night changes in both groups. ASYMP showed a shorter corrected QT and a more reactive vagal modulation leading to significant day-night variations of respiratory sinus arrhythmia. By contrast, SYMP had no significant day-night variations of the vagal control. Conversely, SYMP showed a higher sympathetic control during day compared to ASYMP, having a larger QT variance. These findings suggest that frequency domain HP and QT variability markers can account for the different arrhythmic risk of LQT2 ASYMP and SYMP patients.

Mitral annular disjunction (MAD) is a structural abnormality of the mitral annulus, defined by a detachment of the atrial wall-mitral valvular junction from the left ventricular (LV) free wall. This structural abnormality in mitral annulus fibrosus is significantly associated with the presence of mitral valve prolapse (MVP) [1], but it can be also detected in normal cases as an anatomical variation of the mitral annulus fibrosus [2]. The main tools to detect MAD are echocardiography and cardiac magnetic resonance. Prevalence of MAD in the general population ranges from 7% [1] to 9% [2]. Several studies proved an association between MAD and arrhythmic events, independently of concomitant mitral valve abnormalities, suggesting the existence of a novel entity: MAD arrhythmic syndrome [3]. Herein we describe a case report of a middle age man with MAD who experienced ventricular arrhythmias and placement of an implantable cardioverter-defibrillator (ICD).

Objectives This study sought to investigate whether shape-based late gadolinium enhancement (LGE) metrics and simulations of re-entrant electrical activity are associated with arrhythmic events in patients with nonischemic dilated cardiomyopathy (NIDCM). Background The presence of LGE predicts life-threatening ventricular arrhythmias in NIDCM; however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information. Methods Cardiac magnetic resonance (CMR)-LGE shape metrics were computed for a cohort of 156 patients with NIDCM and visible LGE and tested retrospectively for an association with an arrhythmic composite endpoint of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for re-entry induction in each patient’s scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations. Results During a median follow-up of 1,611 (interquartile range: 881 to 2,341) days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE–myocardial interface area (hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.24 to 2.47; p = 0.001), number of simulated re-entries (HR: 1.40; 95% CI: 1.23 to 1.59; p, Central Illustration

Background Ventricular arrhythmic events are responsible for 50% of death in heart failure but no reliable predictive marker is known to discriminate patients at risk of fatal arrhythmia. Interestingly, familial predisposition has been reported suggesting a role of genetic factors. Purpose Identify genetic markers increasing the arrhythmic risk in heart failure population. Method We prospectively included heart failure patients with left ventricular ejection fraction (LVEF) under 35% and a cardioverter defibrillator in primary prevention in 22 French centres between 2009 and 2017. Patients were followed for 72 months and divided into two groups: cases with an arrhythmic event during follow-up and controls. A Genome Wide Association Study (GWAS) was done. Single Nucleotide Polymorphisms (SNPs) genotyping was performed on Affymetrix Axiom Precision Medicine Research Array plates. To complement the directly genotyped SNPs we performed large-scale imputation based on the Haplotype Reference Consortium European ancestry panel leading to a dataset of 7,5 million of SNPs. Results 332 cases and 567 controls were included (86% men, mean age at implantation 52±11 years). 78% of patients had ischaemic cardiopathy, 20% had dilated cardiomyopathy. Mean LVEF was 27±5%. No statistical difference was found between cases and controls on clinical parameters, biological results, electrocardiographic measures. No locus shows genome-wide significant association (p Conclusion No locus raises genome-wide significance, but several signals with a nominal p-value point to relevant genes and pathways. Replication of the GWAS is ongoing on a cohort of 156 new patients with a less severe cardiopathy implanted with a cardioverter defibrillator in secondary prevention. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Nantes University Hospital

Background Although some post myocardial infarction (post-MI) and dilated cardiomyopathy (DCM) patients with mid-range ejection fraction heart failure (HFmrEF = 40–49%) face an increased risk for arrhythmic Sudden Cardiac Death (SCD), current guidelines do not recommend an implantable cardioverter-defibrillator (ICD). Purpose To assess the accuracy of a novel multifactorial two-step approach, with noninvasive risk factors (NIRFs) leading to programmed ventricular stimulation (PVS), for SCD risk stratification of hospitalized HFmrEF patients. Methods Forty-eight patients (male=83%, age = 64±14 years, LVEF = 45±5%, ischemic coronary disease = 69%) underwent a NIRF presence screening first step with ECG, SAECG, echocardiography and 24 hour ambulatory ECG (Holter). Thirty-two patients with presence of one out of three NIRFs (SAECG ≥2 positive criteria for late potentials, ventricular premature beats ≥240/24 hours, and ≥1 episode of non-sustained ventricular tachycardia on Holter) were further stratified with PVS. Patients were classified as either low (Group 1, n=16, NIRFs−), moderate (Group 2, n=18, NIRFs+ /PVS−) or high risk (Group 3, n=14, NIRFs+/PVS+). All Group 3 patients received an ICD. Results After 41±18 months, 9 out of 48 patients experienced the major arrhythmic event (MAE) endpoint (clinical ventricular tachycardia/fibrillation = 3, appropriate ICD activation = 6). The endpoint occurred more frequently in Group 3 (7/14, 50%) than in Groups 1 & 2 (2/34, 5.8%). A logistic regression model adjusted for PVS, age and LVEF revealed that PVS was an independent MAE predictor (OR: 21.152, 95% CI: 2.618–170.887, p=0.004). Kaplan Meier curves diverged significantly (p logrank Conclusion In hospitalized HFmrEF post-MI and DCM patients, a NIRFs leading to PVS two-step approach efficiently detected the subgroup at increased risk for MAEs. Funding Acknowledgement Type of funding source: None

ObjectivesThis study sought to investigate whether shape-based late gadolinium enhancement (LGE) metrics and simulations of re-entrant electrical activity are associated with arrhythmic events in patients with nonischemic dilated cardiomyopathy (NIDCM).BackgroundThe presence of LGE predicts life-threatening ventricular arrhythmias in NIDCM; however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information.MethodsCardiac magnetic resonance (CMR)-LGE shape metrics were computed for a cohort of 156 patients with NIDCM and visible LGE and tested retrospectively for an association with an arrhythmic composite endpoint of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for re-entry induction in each patient’s scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations.ResultsDuring a median follow-up of 1,611 (interquartile range: 881 to 2,341) days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE–myocardial interface area (hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.24 to 2.47; p = 0.001), number of simulated re-entries (HR: 1.40; 95% CI: 1.23 to 1.59; p ConclusionsThe area of interface between scar and surviving myocardium, as well as simulated re-entrant activity, are associated with an elevated risk of major arrhythmic events in patients with NIDCM and LGE and represent novel risk predictors.

BACKGROUND: The presence of late-gadolinium enhancement (LGE) predicts life threatening ventricular arrhythmias in non-ischemic dilated cardiomyopathy (NIDCM); however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information. OBJECTIVE: This study sought to investigate whether shape-based LGE metrics and simulations of reentrant electrical activity are associated with arrhythmic events in NIDCM patients. METHODS: CMR-LGE shape metrics were computed for a cohort of 156 NIDCM patients with visible LGE and tested retrospectively for an association with an arrhythmic composite end-point of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for reentry induction in each patient’s scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations. RESULTS: During a median follow-up of 1611 [IQR 881-2341] days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE-myocardial interface area (HR:1.75; 95% CI:1.24-2.47; p=0.001), number of simulated reentries (HR: 1.4; 95% CI: 1.23-1.59; p

Summary There is an increasing expectation that computational approaches may supplement existing human decision-making. Frontloading of models for cardiac safety prediction is no exception to this trend, and ongoing regulatory initiatives propose use of high-throughput in vitro data combined with computational models for calculating proarrhythmic risk. Evaluation of these models requires robust assessment of the outcomes. Using FDA Adverse Event Reporting System reports and electronic healthcare claims data from the Truven-MarketScan US claims database, we quantify the incidence rate of arrhythmia in patients and how this changes depending on patient characteristics. First, we propose that such datasets are a complementary resource for determining relative drug risk and assessing the performance of cardiac safety models for regulatory use. Second, the results suggest important determinants for appropriate stratification of patients and evaluation of additional drug risk in prescribing and clinical support algorithms and for precision health., Graphical Abstract, Highlights In vitro data and computational models can assist with calculating pro-arrhythmic risk We use patient health records and FDA Adverse Event Reporting System reports Use of such datasets helps assess relative drug risk and cardiac safety models We quantify how patient characteristics can affect arrhythmia incidence, Davies et al. analyze patient health records and FDA Adverse Event Reporting System reports to demonstrate how patient subtypes affect the incidence of drug-related arrhythmia. Using such real-world data to understand background arrhythmia can further validate cardiac risk models for regulatory use and help stratify patients when evaluating drug risk.

Background: Ischemic cardiomyopathy is associated with an increased risk of sudden death, activation of the unfolded protein response (UPR), and reductions in multiple cardiac ion channels and transporters. When activated, the protein kinase-like ER kinase (PERK) arm of the unfolded protein response (UPR) reduces protein translation and abundance. We hypothesize that inhibition of PERK could prevent cardiac ion channel downregulation and reduce arrhythmic risk after myocardial infarct (MI). Methods: The MI mouse model was induced by a left anterior descending coronary artery ligation. Pharmacological inhibition of PERK was achieved with a specific inhibitor, GSK2606414. Genetic inhibition of PERK was achieved by cardiac-specific PERK knockout in C57BL/6J mice (PERKKO). Echocardiography, telemetry, and electrophysiological measurements were performed to monitor cardiac function and arrhythmias. Results: Three weeks after surgery, the wild type MI mice exhibited decreased ejection fraction (EF%), ventricular tachycardia (VT) and prolonged QTc intervals. The UPR effectors (phospho-PERK, phospho-IRE1, and ATF6N) were elevated significantly (1.7- to 5.9-fold) at protein levels, and all major cardiac ion channels showed decreased protein expression in MI hearts. MI cardiomyocytes showed decreased currents for all major channels (I Na , I CaL , I to , I K1 , and I Kur : 60±6%, 53±9%, 27±6%, 55±7%, and 40±7% of sham, respectively, P90 : 291±43 ms of MI vs. 100±12 ms of sham, Pmax : 95±4 V/s of MI vs. 132±6 ms of sham, PNa and I to , shortened APD, and increased dV/dt max . PERKKO mice exhibited reduced electrical remodeling in response to MI with shortened QTc intervals, less VT episodes, and higher survival rates. Conclusion: PERK is activated during MI and contributes to arrhythmic risk by downregulation of select cardiac ion channels. PERK inhibition prevented these changes and reduced arrhythmic risk. These results suggest that ion channel downregulation during MI is a fundamental arrhythmic mechanism and maintaining ion channel levels is antiarrhythmic.

Introduction Recently, the presence of right bundle brunch block (RBBB) in patients with persistent ischaemic symptoms has been suggested as an indication for emergent coronary angiography. Objective The aim of this study was to assess the prognostic impact of RBBB in patients with acute myocardial infarction (AMI) before the implementation of the recent recommendations. Methods We retrospectively studied consecutive patients admitted with AMI between 2011 and 2013. Patients with left bundle brunch block, pacemaker, or nonspecific intraventricular conduction delay were excluded. Patients with RBBB were compared with those without RBBB. Clinical characteristics, in-hospital evolution, and major adverse cardiovascular events (MACE) during follow-up, defined as cardiovascular death, sustained ventricular arrhythmias, acute heart failure syndromes, recurrent myocardial infarction, or acute stroke, were analysed. Results The analysis included 481 patients. Thirty two patients (6.7%) had RBBB. Patients with RBBB were older. During hospital admission, RBBB patients had a higher rate of sustained ventricular tachycardia and death. Survival curve analysis showed that patients with RBBB had a lower in-hospital survival rate (Log-rank, p = 0.004). After discharge, during a mean follow-up time of 24.3 ± 11.6 months, 53 patients (12%) died. Survival curve analysis showed a lower survival rate free of MACE for those patients with RBBB (Log-rank, p = 0.011). RBBB was independently associated with MACE occurrence (HR 2.17, 95% CI 1.07–4.43; p = 0.033), after adjusting for demographic data, coronary angiography findings, treatment performed, echocardiographic evaluation, and medical therapy. Conclusion Patients with RBBB had a higher rate of in-hospital mortality and arrhythmic events, and an increased risk of MACE during follow-up.

Patients with scar-associated fibrotic tissue remodelling are at greater risk of ventricular arrhythmic events, but current methods to detect the presence of such remodelling require invasive procedures. We present here a potential method to detect the presence, location and dimensions of scar using pacing-dependent changes in the vectorcardiogram (VCG). Using a clinically-derived whole-torso computational model, simulations were conducted at both slow and rapid pacing for a variety of scar patterns within the myocardium, with various VCG-derived metrics being calculated, with changes in these metrics being assessed for their ability to discern the presence and size of scar. Our results indicate that differences in the dipole angle at the end of the QRS complex and differences in the QRS area and duration may be used to predict scar properties. Using machine learning techniques, we were also able to predict the location of the scar to high accuracy, using only these VCG-derived rate-dependent changes as input. Such a non-invasive predictive tool for the presence of scar represents a potentially useful clinical tool for identifying patients at arrhythmic risk., Graphical abstract, Highlights • Non-invasive assessment of scar arrhythmic risk remains a significant challenge. • Rate-dependent changes in vectorcardiograms convey the functional presence of scar. • Random forest machine-learning allows high accuracy for determining scar location.

Early after-depolarizations (EADs) are action potential (AP) repolarization abnormalities that can trigger lethal arrhythmias. Simulations using biophysically-detailed cardiac myocyte models can reveal how model parameters influence the probability of these cellular arrhythmias, however such analyses can pose a huge computational burden. We have previously developed a highly simplified approach in which logistic regression models (LRMs) map parameters of complex cell models to the probability of ectopic beats (EBs). Here, we extend this approach to predict the probability of early after-depolarizations (P(EAD)). We use the LRM to investigate how changes in parameters of the slow-activating delayed rectifier current (IKs) affect P(EAD) for 17 different Long QT syndrome type 1 (LQTS1) mutations. We compare P(EAD) for these 17 LQTS1 mutations with two other recently proposed model-based arrhythmia risk metrics. These three model-based risk metrics yield similar prediction performance; however, they all fail to predict relative clinical risk for a significant number of the 17 studied LQTS1 mutations. The consistent successes and failures of all three risk metrics suggest that important functional characteristics of LQTS1 mutations may not yet be fully known.Author summaryAn early after-depolarization (EAD) is an abnormal cellular electrical event which can trigger dangerous arrhythmias in the heart. We use our previously developed method to build a simple logistic regression model (LRM) that estimates the probability of EAD (P(EAD)) as a function of myocyte model parameters. Using this LRM along with two other recently published model-based arrhythmia risk predictors, we estimate risk of arrhythmia for 17 Long QT syndrome type 1 (LQTS1) mutations. Results show that all approaches have similar prediction performance in that there are a set of mutations whose relative clinical risk for arrhythmia are well estimated using these metrics, but that relative risk is consistently over- or under-estimated across all approaches for a significant number of other mutations. We believe this indicates that the functional characterization of the LQTS1 phenotype is incomplete.

BACKGROUND New automated approaches for left heart chamber quantification based on adaptive analytics algorithms have been introduced for both two- (2DE) and three-dimensional (3DE) echocardiography. These algorithms measure a left ventricular ejection fraction (LVEF) and reduce the intra- and inter-observer variability associated with the conventional manual tracing of LV endocardial borders. However, the clinical utility of these algorithms in the sudden cardiac death (SCD) risk stratification of patients with organic heart disease remains to be clarified. PURPOSE We sought to test the feasibility and the accuracy of two automated algorithms that measure 2DE and 3DE LVEF in patients with impaired LV systolic function and to define the cut-off values for fully automated 2DE and 3DE LVEF that could predict major arrhythmic events (MAE). We wanted also to assess the feasibility of replacing manual 2DE and semi-automated (SA) 3DE LVEF with fully-automated (FA) 2DE and 3DE LVEF respectively, in the stratification of high arrhythmic risk patients. METHODS We prospectively enrolled 240 patients (63 ± 13 years, 81% men) with both ischemic and non-ischemic cardiomyopathy with 2DE LVEF < 50%, no previous MAE or coronary artery revascularization < 90 days, after at least 3 months of optimal medical therapy for heart failure. MAE were defined as SCD, resuscitated cardiac arrest (CA), ventricular fibrillation, sustained ventricular tachycardia and appropriate ICD shocks. The risk detection cut-off values for 2DE and 3DE FA LVEF were computed using the maximally selected rank statistics method. In order to predict the risk of MAE we created four different risk models, including both clinical characteristics (age, NYHA class, aetiology of the LV dysfunction) and imaging-derived data (2DE manual LVEF, 2DE FA LVEF, 3DE SA LVEF and 3DE FA LVEF), analyzed by a ROC curve. RESULTS During a 27 ± 25months follow-up period, 31 patients (13%) presented MAE including SCD (n= 22; 9%), resuscitated CA (n = 3; 1%) and appropriate ICD shocks (n = 6; 2%). Both 2DE and 3DE FA LVEF showed high feasibility (92% and 95%, respectively), and good agreement with conventional LVEF (2DE mean difference 4 ± 7%, and 3DE mean difference 4 ± 7%). We identified two FA LVEF cut-offs for the MAE detection: 2DE CONCLUSIONS Both 2DE and 3DE FA LVEF are feasible and accurate alternative to the conventional (manual) or SA endocardial border tracing. The use of specific FA 2DE LVEF cut-off values showed a comparable predictive power in the MAE risk stratification compared to the conventional one with the advantage of very low intra- and inter-observer variability.

Sudden cardiac death and arrhythmia-related events in patients with non-ischaemic dilated cardiomyopathy (NICM) have been significantly reduced over the last couple of decades as a result of evidence-based pharmacological and non-pharmacological therapeutic strategies. Nevertheless, the arrhythmic stratification in patients with NICM remains extremely challenging, and the simple indication based on left ventricular ejection fraction appears to be insufficient. Therefore, clinicians need to go beyond the current criteria for implantable cardioverter-defibrillator implantation in the direction of a multiparametric evaluation of arrhythmic risk. Several parameters for arrhythmic risk stratification, ranging from electrocardiographic, echocardiographic, imaging-derived and genetic markers, are crucial for proper arrhythmic risk stratification and a multiparametric evaluation of risk in patients with NICM. In particular, integration of cardiac magnetic resonance parameters (mostly late gadolinium enhancement) and specific genetic information (ie, presence of LMNA, PLN, FLNC mutations) appears fundamental for proper implementation of the current arrhythmic risk stratification. Finally, a novel approach focused on both arrhythmic risk and prediction of left ventricular reverse remodelling during follow-up might be useful for effective multiparametric and dynamic arrhythmic risk stratification in NICM. In the future, a complete and integrated evaluation might be mandatory to implement arrhythmic risk prediction in patients with NICM and to discriminate the competing risk between heart failure-related events and life-threatening arrhythmias.

Background: In many genetic and acquired non-ischaemic cardiomyopathies (NICM) there have been frequent reports of involvement of the interventricular septum (IVS) by late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR). However, no studies have investigated the relationship between septal LGE and arrhythmias in different NICM subtypes. Methods: This study enrolled 103 patients with septal LGE at baseline CMR and different NICM: hypertrophic (n=29) or lamin A/C gene (LMNA)-associated (n=23) cardiomyopathy, and acute (n=30) or previous (n=21) myocarditis. During follow-up, the occurrences of malignant ventricular arrhythmias (MVA) and major bradyarrhythmias (BA) were evaluated. Results: At 4.9±0.7 years of follow-up, the occurrence of MVA and major BA in genetic vs acquired NICM were 10 of 52 vs 12 of 51, and 10 of 52 vs 4 of 51, respectively (both p=n.s.). However, MVA occurred more frequently in LMNA-NICM (eight of 23 vs two of 29 hypertrophic, p=0.015) and in previous myocarditis (nine of 21 vs three of 30 acute, p=0.016), while major BAs were particularly common in LMNA-NICM patients only (nine of 23 vs one of 29 hypertrophic, p=0.003). Different patterns of septal LGE were consistently retrospectively identified at baseline CMR: junctional and limited to the base in 79.3% of uneventful hypertrophic NICM; extended and focally transmural in LMNA-NICM with follow-up arrhythmias (both p

Introduction Mitral annular disjunction (MAD) is an anatomical variation of the mitral annulus, characterized by an atrial displacement of the leaflet’s hinge points. It is associated with severe ventricular arrhythmias (VA) in mitral valve prolapse (MVP). Purpose The aim of this study was to assess MAD in MVP by echocardiography, analyze the reproducibility of measurements and evaluate its importance for arrhythmic risk stratification along with strain analysis of myocardial deformation. Methods Two hundred and sixty patients with MVP were included. MAD was evaluated and measured by two observers in the parasternal long axis and in the apical views. Myocardial longitudinal strain was analyzed by speckle-tracking. Results Ninety four patients (36.2%) of MVP patients presented MAD. These patients were younger (53.7 ± 15.1 vs 58.4 ± 17.6, p = 0.033) with higher rate of atypical chest pain (21.3% vs 11.5%, p = 0,041) and bileaflet prolapse (50.5% vs 32.3%, p = 0.004). Para-sternal long-axis view was the incidence of choice to detect MAD with a moderate inter-observer concordance (Kappa of 0.55), good correlation (r = 0.69, p Conclusion No significant association was found between severe VA and the presence or severity of MAD in MVP patients. Increased mechanical dispersion and reduced global longitudinal strain may be helpful for arrhythmic risk stratification. Abstract P668 Figure. Comparison of MD and GLS

International audience; Purpose of review: Degenerative mitral regurgitation (DMR) continues to be an important cause of morbidity and mortality with surgical mitral valve repair remaining the gold standard for the treatment of severe disease. The purpose of this review is to summarize recent advances in the understanding of DMR as well as the progress made in its assessment with a focus on imaging techniques.Recent findings: Recent insights into the anatomy and physiology of DMR challenge the assumption that fibroelastic deficiency and Barlow disease are part of a single DMR spectrum. Advances in echocardiography and cardiovascular MRI have the potential to improve quantification of mitral regurgitation, provide unique information on prognosis and impact of DMR, further the association between DMR and arrhythmic risk and aide in decision-making for DMR treatment.Summary: With growing interest in the use of noninvasive transcatheter therapies in the mitral valve space, comprehensive assessment of the mitral valve is critical to instruct decision-making and guide therapeutic strategy.

BACKGROUND: Measuring repolarization characteristics is challenging and has been reserved for experienced physicians. In electrocardiographic imaging (ECGI), activation-recovery interval (ARI) is used as a measure of local cardiac repolarization duration. We hypothesized that repolarization characteristics, such as local electrogram morphology and local and global dispersion of repolarization timing and duration could be of significance in ECGI.OBJECTIVE: To further explore their potential in arrhythmic risk stratification we investigated the use of novel repolarization parameters in ECGI.MATERIALS AND METHODS: We developed and compared methods for T-peak and T-end detection in reconstructed potentials. All methods were validated on annotated reconstructed electrograms (EGMs). Characteristics of the reconstructed EGMs and epicardial substrate maps in IVF patients were analyzed by using data recorded during sinus rhythm. The ECGI data were analyzed for EGM morphology, conduction, and repolarization.RESULTS: We acquired ECGI data from 8 subjects for this study. In all patients we evaluated four repolarization parameters: Repolarization time, T-wave area, Tpeak-Tend interval, and T-wave alternans. Most prominent findings were steep repolarization time gradients in regions with flat EGMs. These regions were also characterized by low T-wave area and large differences in Tpeak-Tend interval.CONCLUSIONS: Measuring novel repolarization parameters in reconstructed electrograms acquired with ECGI is feasible, can be done in a fully automated manner and may provide additional information on underlying arrhythmogenic substrate for risk stratification. Further studies are needed to investigate their potential use and clinical application.

The prevalance of depression and anxiety is higher at the patients diagnosticated with viral liver disease. The corelation between stress and chronic liver disease is a natural, implicit one, but still insufficiently studied. The study has the objective of finding out the clinical and also biochemical correlations between stress and chronic viral diseases. Our research was realised on a group of 78 patients with chronic viral liver disease, who underwent an evaluation of the stress level, both from a subjective point of view and based on concrete methods like questionnaires. The patients were asked to espress their state more or less affected by stress, and, subsequently, they were subjected to a questionnaire that was analyzed, followed by establishing the necessary correlations. Our patients were also evaluated by cardiologicaly, psychologicaly and psyhiatricaly examinations. After the first evaluation we had these results :38 patients (49.19%) consider that they have an average stress level, 18 patients (22.58%) have a high stress level. Only 22 patients (28.22%) declared stress was at a low level. We divided the pacients in two groups, function of Qt (questionare total score) results and we observed that a number of 38 patients ( 49.19%) registered �Qt 20 and 40 patients (50.81%) had Qt � 20, 63 patients (50.81%).We found a strong correlation between the patients� subjective evaluation of the stress level and the objective evaluation of stress level according to the used questionnaire, which confirms the objectivity of our study. We found a direct corelation, with a morphological, biochemical and functional support between stress and the arrhythmia risk in the evolution of chronic liver disease. We consider very important a complex examination psychiatricaly, psychologicaly and cardiological of the pacients diagnosticated with viral liver disease in order to help them and to prevent arrhythmic events, depression, anxiety and other mood disorders.