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This article summarizes the main electrocardiogram (ECG) findings in dilated cardiomyopathy (DCM) patients. Recent reports are described in the great ‘pot’ of DCM peculiar ECG patterns that are typical of specific forms of DCM. Patients with late gadolinium enhancement on CMR, who are at greatest arrhythmic risk, have also distinctive ECG features. Future studies in large DCM populations should evaluate the diagnostic and prognostic value of the ECG.

Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by deficient a-galactosidase A activity that leads to an accumulation of glycolipids, mainly globotriaosylceramide (Gb3) and globotriaosylsphingosine, in affected tissues, including the heart. Cardiovascular involvement usually manifests as left ventricular hypertrophy (LVH), myocardial fibrosis, heart failure, and arrhythmias, which limit the quality of life and represent the most common causes of death. Following the introduction of enzyme replacement therapy, early diagnosis and treatment have become essential in slowing down the disease progression and preventing major cardiac complications. Recent advances in the understanding of FD pathophysiology suggest that in addition to Gb3 accumulation, other mechanisms contribute to the development of cardiac damage. FD cardiomyopathy is characterized by an earlier stage of glycosphingolipid accumulation and a later one of hypertrophy. Morphological and functional aspects are not specific in the echocardiographic evaluation of Anderson–Fabry disease. Cardiac magnetic resonance with tissue characterization capability is an accurate technique for the differential diagnosis of LVH. Progress in imaging techniques has improved the diagnosis and staging of FD-related cardiac disease: a decreased myocardial T1 value is specific of FD. Late gadolinium enhancement is typical of the later stage of cardiac involvement but as in other cardiomyopathy is also valuable to predict the outcome and cardiac response to therapy.

Criteria for diagnosis of arrhythmogenic cardiomyopathy (ACM) were first proposed in 1994 and subsequently revised in 2010 and in 2020 by an international task force. According to the last consensus of 2020, ACM is defined as a heart muscle disease affecting right ventricle, left ventricle or both, whose principal pathologic feature is fibrofatty myocardial replacement that impairs systolic ventricular function and predisposes to lethal ventricular arrhythmias. ECG findings not only could help to early recognize affected patients but also could identify the ones with maximum risk of ventricular arrhythmias and sudden cardiac death.

Heart failure (HF) is a major and still growing medical problem and is characterized by episodes of acute decompensation that are associated with a negative prognosis and a significant burden on the patients, doctors, and healthcare resources. Early detection of incipient HF may allow outpatient treatment before patients severely decompensate, thus reducing HF hospitalizations and related costs. The HeartLogic™ algorithm is an automatic, remotely managed system combining data directly related to HF pathophysiology into a single score, the HeartLogic™ index. This index proved to be effective in predicting the risk of incipient HF decompensation, allowing to redistribute resources from low-risk to high-risk patients in a timely and cost-saving manner. The alert-based remote management system seems more efficient than the one based on scheduled remote transmission in terms of caregivers’ workload and alert detection timing. The widespread application of the HeartLogic™ algorithm requires the resolution of logistical and financial issues and the adoption of a pre-defined, functional workflow. In this paper, we reviewed general aspects of remote monitoring in HF patients, the functioning and pathophysiological basis of the HeartLogic index, its efficiency in the management of HF patients, and the economic effects and the organizational revolution associated with its use.

Sudden cardiac death (SCD) can be caused by several clinical conditions, overt or misconceived, which recognize different pathophysiologies determining the development of fatal arrhythmic events. In the various forms of structural heart disease such as ischaemic heart disease, cardiomyopathies (e.g. hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic cardiomyopathy), channelopathies (e.g. long-QT syndrome, congenital short QT, Brugada syndrome, early repolarization (ER) syndrome, and idiopathic ventricular fibrillation) but also in the apparently healthy subject, the 12-lead electrocardiogram (ECG) has proved, over the years, to be a reliable and readily available method for stratifying the risk of adverse arrhythmic events and consequently SCD. Several electrocardiographic markers have been shown to be associated with adverse outcomes in different types of patients. Although with different sensitivity and specificity in each clinical condition, depolarization abnormalities, such as QRS fragmentation, Q waves, QRS duration, left posterior fascicular block, low QRS voltage, and left ventricular hypertrophy and similarly repolarization abnormalities as ER pattern, T wave alternans, QT interval, and QT dispersion, have shown significant efficacy in predicting SCD. Despite the advancement of techniques especially in the field of imaging, the correct interpretation of the 12-lead ECG remains, therefore, an effective tool for assessing the possible prognostic outcome in terms of arrhythmic risk and SCD in different types of patients.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus. In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%. Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC. P.J. is supported by the Daniel Bravo Foundation grant and Spanish Society of Cardiology Magda Heras mobility grant, A.G. by the Wilton W. Webster Fellow of Heart Rhythm Society, The Johns Hopkins ARVD/C Programme by the Leonie-Wild Foundation, Leyla Erkan Family Fund for ARVD Research, The Hugh Calkins, Marvin H. Weiner, and Jacqueline J. Bernstein Cardiac Arrhythmia Center, Dr Francis P. Chiramonte Private Foundation, Dr Satish, Rupal, and Robin Shah ARVD Fund at Johns Hopkins, Bogle Foundation, Campanella Family, Patrick J. Harrison Family, Peter French Memorial Foundation, and Wilmerding Endowments, H.K.J. by grants from Novo Nordisk Foundation, Denmark (NNF18OC0031258 and NNF20OC0065151), S.A.L. by NIH grant 1R01HL139731 and American Heart Association 18SFRN34250007, R.T. by the Canada Research Chairs programme, J.C.T. by the Philippa and Marvin Carsley Cardiology Research Chair. S.G.P. receives support from Ricerca Corrente funding scheme of the Italian Ministry of Health and Italian Ministry of Research and University Dipartimenti di Eccellenza 2018 to 2022 grant to the Molecular Medicine Department (University of Pavia). Sí

HeartLogic algorithm combines data from multiple implantable defibrillators (ICD)-based sensors to predict impending heart failure (HF) decompensation. A treatment protocol to manage algorithm alerts is not yet known, although decongestive treatment adjustments are the most frequent alert-triggered actions reported in clinical practice. We describe the implementation of HeartLogic for remote monitoring of HF patients, and we evaluate the approach to diuretic dosing and timing of the intervention in patients with device alerts.The algorithm was activated in 229 ICD patients at eight centers. The median follow-up was 17 months (25th-75th percentile: 11-24). Remote data reviews and patient phone contacts were undertaken at the time of HeartLogic alerts, to assess the patient's status and to prevent HF worsening. We analyzed alert-triggered augmented HF treatments, consisting of isolated increases in diuretics dosage.We reported 242 alerts (0.8 alerts/patient-year) in 123 patients, 137 (56%) alerts triggered clinical actions to treat HF. The HeartLogic index decreased after the 56 actions consisting of diuretics increase. Specifically, alerts resolved more quickly when the increases in dosing of diuretics were early rather than late: 28 days versus 62 days, p .001. The need of hospitalization for further treatments to resolve the alert condition was associated with higher HeartLogic index values on the day of the diuretics increase (odds ratio: 1.11, 95% CI: 1.02-1.20, p = .013) and with late interventions (odds ratio: 5.11, 95% CI: 1.09-24.48, p = .041). No complications were reported after drug adjustments.Decongestive treatment adjustments triggered by alerts seem safe and effective. The early use of decongestive treatment and the use of high doses of diuretics seem to be associated with more favorable outcomes.

AimsLow QRS voltages (LQRSV) are an unexpected finding in left ventricular hypertrophy, i.e. hypertrophic cardiomyopathy (HCM) or athlete’s heart.Methods and resultsPrevalence and clinical correlates of LQRSV were investigated in 197 consecutive HCM patients, aged 58 ± 13 years and comparatively in 771 Olympic athletes, aged 23 ± 4. Clinical characterization included family/personal history, symptoms, New York Heart Association (NYHA) functional class, electrocardiographic pattern, ventricular arrhythmias, and cardiac magnetic resonance (CMR). Twenty-two (11%) of HCM and 18 (2.3%) of athletes presented LQRSV. At initial evaluation, in HCM, LQRSV showed no differences vs. non-LQRSV for functional class (90% vs. 91%, in Classes I and II; P = 0.983), symptoms (27% vs. 18%; P = 0.478), and ventricular arrhythmias (40% vs. 39%; P = 857) but showed larger extent of late gadolinium enhancement (LGE) at CMR (4.1 ± 1.5 vs. 1.5 ± 0.7 affected segments; P < 0.001). In athletes, LQRSV was associated with larger prevalence of inverted T-waves (22% vs. 9%; P < 0.001) and ventricular arrhythmias (28% vs. 8%; P = 0.005). In one LQRSV athlete, arrhythmogenic cardiomyopathy was identified. Over 4.5 ± 2.6-year follow-up, presence of LQRSV in HCM was associated with larger incidence of functional deterioration (31% vs. 14%; P = 0.038), stroke (22% vs. 6%; P = 0.008), and implantable cardioverter defibrillator (ICD) implant (27% vs. 10%; P = 0.015). No clinical events occurred in LQRSV athletes without initial evidence of cardiac disease.ConclusionLQRSV are relatively common (11%) in HCM and have clinical relevance, being predictive over a medium term for a worsening functional class, incidence of stroke, and ICD implant. Instead, LQRSV are rare (2.3%) in athletes but may occasionally be a marker that raises suspicion for underlying cardiac disease at risk.

Variants in desmoplakin gene (DSP MIM *125647) have been usually associated with Arrhythmogenic Cardiomyopathy (ACM), or Dilated Cardiomyopathy (DCM) inherited in an autosomal dominant manner. A cohort of 18 probands, characterized as heterozygotes for DSP variants by a target Next Generation Sequencing (NGS) cardiomyopathy panel, was analyzed. Cardiological, genetic data, and imaging features were retrospectively collected. A total of 16 DSP heterozygous pathogenic or likely pathogenic variants were identified, 75% (n = 12) truncating variants, n = 2 missense variants, n = 1 splicing variant, and n = 1 duplication variant. The mean age at diagnosis was 40.61 years (IQR 31–47.25), 61% of patients being asymptomatic (n = 11, New York Heart Association (NYHA) class I) and 39% mildly symptomatic (n = 7, NYHA class II). Notably, 39% of patients (n = 7) presented with a clinical history of presumed myocarditis episodes, characterized by chest pain, myocardial enzyme release, 12-lead electrocardiogram abnormalities with normal coronary arteries, which were recurrent in 57% of cases (n = 4). About half of the patients (55%, n = 10) presented with a varied degree of left ventricular enlargement (LVE), four showing biventricular involvement. Eleven patients (61%) underwent implantable cardioverter defibrillator (ICD) implantation, with a mean age of 46.81 years (IQR 36.00–64.00). Cardiac magnetic resonance imaging (CMRI) identified in all 18 patients a delayed enhancement (DE) area consistent with left ventricular (LV) myocardial fibrosis, with a larger localization and extent in patients presenting with recurrent episodes of myocardial injury. These clinical and genetic data confirm that DSP-related cardiomyopathy may represent a distinct clinical entity characterized by a high arrhythmic burden, variable degrees of LVE, Late Gadolinium Enhancement (LGE) with subepicardial distribution and episodes of myocarditis-like picture.

Historically, regular exercise contributed to reduce the arrhythmic burden and improve cardiovascular outcomes in the general population. However, a heightened risk of atrial fibrillation (AF) seems to occur mainly amongst endurance athletes. The exact mechanisms are not fully elucidated, but dynamic interactions between electro-anatomical changes induced by exercise, the autonomic system, variable triggers, along individual genetic predisposition are the main contributors to AF development in athletes. The type and training load of sports are also crucial in determining the arrhythmogenic milieu predisposing to AF insurgence and perpetuation. Moreover, a sex difference seems to influence an increased risk of AF only in men undergoing strenuous exercise, whereas women appear protected even during more vigorous training. In the absence of solid evidence, the advent of modern technologies could help to monitor and deep investigate the peculiar aspects of AF in these athletes. This review aims to describe the pathophysiology, diagnosis, and management of AF in athletes, shedding light on possible future strategies to face AF in this population.

The autonomic nervous system (ANS) is known to play an important role in the genesis and maintenance of atrial fibrillation (AF). Biomolecular and genetic mechanisms, anatomical knowledges with recent diagnostic techniques acquisitions, both invasive and non‐invasive, have enabled greater therapeutic goals in patients affected by AF related to ANS imbalance. Catheter ablation of ganglionated plexi (GP) in the left and right atrium has been proposed in varied clinical conditions. Moreover interesting results arise from renal sympathetic denervation and vagal nerve stimulation. Despite all this, in the scenario of ANS modulation translational strategies we necessary must consider the treatment or correction of dynamic factors such as obesity, obstructive sleep apnea, lifestyle, food, and stress. Finally, new antiarrhythmic drugs, gene therapy and “ablatogenomic” could be represent exciting future therapeutic perspectives., Cardioneuroablation and cardioneuromodulation for patients affected by AF related to ANS imbalance.

COVID pandemic emergency has forced changes from traditional in-person visits to application of telemedicine in order to overcome the barriers and to deliver care. COVID-19 has accelerated adoption of digital health. During this time, the distance is itself a prevention tool and the use of technology to deliver healthcare services and information has driven the discovery of mobile and connected health services. Health services should to be prepared to integrate the old model of remote monitoring of CIEDs and adopt new digital tools such as mobile Apps and connected sensors.

Several reports have focused on biatrial ganglionated plexi (GP) transcatheter ablation to treat cardioinhibitory neurocardiogenic syncope (CNS). Considering that anatomical studies showed a significant number of GP in the right atrium (RA), we hypothesized that RA “cardioneuroablation” could be an effective treatment for CNS. Eighteen consecutive patients (mean age: 36.9 ± 11.2 years) with severe CNS were submitted to transcatheter ablation of GPs in the RA alone using an anatomical approach. Head up tilt test evaluation was performed during the follow-up period at 6, 12, and 24 months and in case of significant symptoms, while heart rate variability parameters were evaluated at patients discharge at 1, 3, 6, 12, 24, and 36 months after ablation. At a mean follow-up of 34.1 ± 6.1 months, 3 (16.6%) patients experienced syncopal episodes and 5 patients (27.7%) only prodromal episodes. Syncopal and prodromal recurrences were significantly decreased both in overall population (P = 0.001) and in symptomatic patients after ablation (P = 0.003). Heart rate variability analysis showed the loss of autonomic balance secondary to a reincrease of sympathetic tone after the acute phase faster than vagal tone more evident at 12 months (LF/HF vs preablation, P

Background Several ECG voltage criteria have been proposed for the diagnosis of left ventricular hypertrophy (LVH). Notably, ECG criteria have been historically validated in concentric LVH but not in hypertrophic cardiomyopathy (HCM), wherein the hypertrophy pattern is typically asymmetric. Objectives The aim of our study was to evaluate the performance of ECG voltage criteria for LVH diagnosis in the HCM population. Material and methods The electrocardiograms of 92 HCM patients and 41 sex- and age-matched controls were evaluated with the most frequently used ECG voltage criteria for LVH diagnosis. Cardiac magnetic resonance (MRI) was performed in HCM and controls in order to quantify LVH and its distribution. Results In the HCM population, the maximal diagnostic accuracy was achieved by Amplitude total and Amplitude total product criteria (58% for both), while the Cornell Voltage best performed in septal HCM (62%), the Sokolov in aVL and Gubner criteria in apical HCM (79% for both) and the Cornell Voltage and Product in anterior HCM (86% for both). All the ECG voltage criteria showed a poor correlation with left ventricular mass and maximal thickness measured by cardiac MRI. Conclusions In our study, only a few ECG voltage criteria used for the detection of LVH in clinical practice showed an acceptable performance in the HCM population. Further studies are needed to clarify the role of ECG for LVH detection in HCM patients.

IMPORTANCE: A high burden of premature ventricular contractions (PVCs) at disease diagnosis has been associated with an overall higher risk of ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC). Data regarding dynamic modification of PVC burden at follow-up with Holter monitoring and its impact on arrhythmic risk in ARVC are scarce. OBJECTIVE: To describe changes in the PVC burden and to assess whether serial Holter monitoring is dynamically associated with sustained ventricular arrhythmias during follow-up in patients with ARVC. DESIGN, SETTINGS, AND PARTICIPANTS: In this cohort study, patients with a definite ARVC diagnosis, available Holter monitoring results at disease diagnosis, and at least 2 additional results of Holter monitoring during follow-up were enrolled from 6 ARVC registries in North America and Europe. Data were collected from June 1 to September 15, 2021. MAIN OUTCOMES AND MEASURES: The association between prespecified variables retrieved at each Holter monitoring follow-up (ie, overall PVC burden; presence of sudden PVC spikes, defined as absolute increase in PVC burden ≥5000 per 24 hours or a relative ≥75% increase, with an absolute increase of ≥1000 PVCs; presence of nonsustained ventricular tachycardia [NSVT]; and use of β-blockers and class III antiarrhythmic drugs) and sustained ventricular arrhythmias occurring within 12 months after that Holter examination was assessed using a mixed logistical model. RESULTS: In 169 enrolled patients with ARVC (mean [SD] age, 36.3 [15.0] years; 95 men [56.2%]), a total of 723 Holter examinations (median, 4 [IQR, 4-5] per patient) were performed during a median follow-up of 54 (IQR, 42-63) months and detected 75 PVC spikes and 67 sustained ventricular arrhythmias. The PVC burden decreased significantly from the first to the second Holter examination (mean, 2906 [95% CI, 1581-4231] PVCs per 24 hours; P

Aims Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an electrical genetic disease characterized by induction of malignant ventricular arrhythmias during adrenergic stress in structurally normal hearts. CPVT is correlated to syncope or sudden cardiac death (SCD). Usually, it is caused by an autosomal dominant mutation in the cardiac ryanodine receptor (RyR2), an essential gene for Ca2+ homeostasis. Methods and results Our case series refers to: a man (59 years) who came to our attention for a clinical check-up 4 years after implanting bicameral pacemaker at the age of 55 years for complete AV block; and his three sons (E. female 27 years; D. male 25 years; and B. female 17 years) who had evidence of polymorphic non-sustained ventricular tachycardia (NSVT) with increasing effort during stress test. The three sons performed cardiac MRI and underwent genetic test. All three were found to be carriers of the same microdeletion of the RYR 2 gene (1q43- extended for about 49 kb) at the genetic test. They also have non-compacted myocardium at cardiac MRI. The father was also found to be a carrier of the same genetic microdeletion, while the mother was negative to the genetic test. The man was diagnosed to be a carrier of the mutation 4 years after pacemaker implantation. Conclusions Mutation of the RyR2 may have different phenotypic expressions and can be correlated to various clinical manifestations. CPVT is the most common one, and its prompt identification is crucial to prevent subjects from sport-related risks and to plan an efficient therapy. Our case series provides evidence for a careful consideration of such a genetic disorder even in presence of a major AV conduction disease in a relatively young subject. In the present case series, no major adverse events occurred. However, we can, in the aftermath, speculate that if a genetic disorder had been suspected when AV block occurred, a timely diagnosis could have been made earlier also for the sons.

Dilated cardiomyopathy (DCM) refers to a spectrum of heterogeneous myocardial disorders characterized by ventricular dilation and depressed myocardial performance in the absence of hypertension, valvular, congenital, or ischemic heart disease. Mutations in LMNA gene, encoding for lamin A/C, account for 10% of familial DCM. LMNA-related cardiomyopathies are characterized by heterogeneous clinical manifestations that vary from a predominantly structural heart disease, mainly mild-to-moderate left ventricular (LV) dilatation associated or not with conduction system abnormalities, to highly pro-arrhythmic profiles where sudden cardiac death (SCD) occurs as the first manifestation of disease in an apparently normal heart. In the present study, we select, among 77 DCM families referred to our center for genetic counselling and molecular screening, 15 patient heterozygotes for LMNA variants. Segregation analysis in the relatives evidences other eight heterozygous patients. A genotype–phenotype correlation has been performed for symptomatic subjects. Lastly, we perform in vitro functional characterization of two novel LMNA variants using dermal fibroblasts obtained from three heterozygous patients, evidencing significant differences in terms of lamin expression and nuclear morphology. Due to the high risk of SCD that characterizes patients with lamin A/C cardiomyopathy, genetic testing for LMNA gene variants is highly recommended when there is suspicion of laminopathy.

Background The early diagnosis of cardiac abnormalities in young athletes may be helpful not only to identify subjects potentially at risk of sudden cardiac death but also to prevent stress-related cardiac dysfunction and cardiovascular events during the life of these subjects. The aim of our study was to investigate the prevalence of cardiac abnormalities in a population of young male soccer players undergoing pre-participation screening through electrocardiogram and trans-thoracic echocardiography. Methods All consecutive male football players undergoing pre-participation screening comprehensive of medical history, physical examination, 12-lead electrocardiogram and trans-thoracic echocardiography at the FMSI Sport Medicine Institute in Rome between January 2008–March 2009 were enrolled in the study. Results Overall, 2261 consecutive young athletes aged 12.4 ± 2.6 years were evaluated. Training-unrelated electrocardiogram abnormalities were observed in 65 (2.9%) athletes. Abnormal trans-thoracic echocardiography was observed in 102 athletes (4.5%), including two cases of hypertrophic cardiomyopathy, eight of mild left ventricular hypertrophy, six of mild left ventricular dilation and 17 of bicuspid aortic valve. An abnormal electrocardiogram was associated with anomalous trans-thoracic echocardiography in 11/65 (16.9%) cases. All athletes requiring sport disqualification were identified by electrocardiogram. Notably, among 2216 athletes with a normal electrocardiogram, 91 had abnormal trans-thoracic echocardiography, including six cases of left ventricular dilation and six of ventricular hypertrophy. Conclusions In a wide population of peri-pubertal male athletes, evaluation of the electrocardiogram identified all cardiac diseases requiring sport disqualification. Trans-thoracic echocardiography alone allowed the identification of cardiac abnormalities potentially leading to cardiomyopathies or major cardiovascular events over time.

Background: Arrhythmogenic Cardiomyopathy (ACM) is a disease of the cardiac muscle, characterized by frequent ventricular arrhythmias and functional/ structural abnormalities, mainly of the right ventricle. To date, 20 different genes have been associated with ACM and the majority of them encode for desmosomal proteins. In this study, we describe the characterization of two novel variants in MHY7 gene, segregating in two ACM families. MYH7 encodes for myosin heavy chain β (MHC-β) isoform, involved in cardiac muscle contractility. Method and Results: In family A, the autopsy revealed ACM with biventricular involvement in both the proband and his father. In family B, the proband had been diagnosed as affected by ACM and implanted with implantable cardioverter defibrillator (ICD), due to ECG evidence of monomorphic ventricular tachycardia after syncope. After clinical evaluation, a molecular diagnosis was performed using a NGS custom panel. The two novel variants identified predicted damaging, located in a highly conserved domain: c. 2630T&gt, C is not described while c.2609G&gt, A has a frequency of 0.00000398. In silico analyses evaluated the docking characteristics between proteins using the Haddock2.2 webserver. Conclusions: Our results reveal two variants in sarcomeric genes to be the molecular cause of ACM, further increasing the genetic heterogeneity of the disease, in fact, sarcomeric variants are usually associated with HCM phenotype. Studies on the role of sarcomere genes in the pathogenesis of ACM are surely recommended in those ACM patients negative for desmosomal mutation screening.

Aim The aim of our study was to compare ivabradine versus bisoprolol in the short-term and long-term treatment of inappropriate sinus tachycardia. Methods From this prospective, parallel-group, open-label study, consecutive patients affected by inappropriate sinus tachycardia received ivabradine or bisoprolol and were evaluated with Holter ECG, ECG stress test, European Heart Rhythm Association score and Minnesota Living With Heart Failure Questionnaire at baseline, after 3 and 24 months. Results Overall, 40 patients were enrolled. Baseline parameters were comparable in the ivabradine and bisoprolol subgroups. Two patients had transient phosphenes with ivabradine and two others interrupted the drug after 3 months as they planned to become pregnant. Eight individuals treated with bisoprolol experienced hypotension and weakness, which caused drug discontinuation in five of them. Ivabradine was superior to bisoprolol in reducing Holter ECG mean heart rate (HR) and mean HR during daytime at short- and long-term follow-up. Moreover, ivabradine but not bisoprolol significantly reduced Holter ECG mean HR during night-time as well as maximal and minimal HR and significantly increased the time duration and maximal load reached at ECG stress test. The quality of life questionnaires significantly improved in both subgroups. Conclusion This study suggests that ivabradine is better tolerated than bisoprolol and seems to be superior in controlling the heart rate and improving exercise capacity in a small population of individuals affected by inappropriate sinus tachycardia during a short-term and long-term follow-up.

Background: Arrhythmogenic Cardiomyopathy (ACM) is a disease of the cardiac muscle, characterized by frequent ventricular arrhythmias and functional/ structural abnormalities, mainly of the right ventricle. To date, 20 different genes have been associated with ACM and the majority of them encode for desmosomal proteins. In this study, we describe the characterization of two novel variants in MHY7 gene, segregating in two ACM families. MYH7 encodes for myosin heavy chain β (MHC-β) isoform, involved in cardiac muscle contractility. Method and Results: In family A, the autopsy revealed ACM with biventricular involvement in both the proband and his father. In family B, the proband had been diagnosed as affected by ACM and implanted with implantable cardioverter defibrillator (ICD), due to ECG evidence of monomorphic ventricular tachycardia after syncope. After clinical evaluation, a molecular diagnosis was performed using a NGS custom panel. The two novel variants identified predicted damaging, located in a highly conserved domain: c. 2630T>C is not described while c.2609G>A has a frequency of 0.00000398. In silico analyses evaluated the docking characteristics between proteins using the Haddock2.2 webserver. Conclusions: Our results reveal two variants in sarcomeric genes to be the molecular cause of ACM, further increasing the genetic heterogeneity of the disease; in fact, sarcomeric variants are usually associated with HCM phenotype. Studies on the role of sarcomere genes in the pathogenesis of ACM are surely recommended in those ACM patients negative for desmosomal mutation screening.

BackgroundIn athletes with ventricular arrhythmias (VA) and otherwise unremarkable clinical findings, cardiac magnetic resonance (CMR) may reveal concealed pathological substrates. The aim of this multicenter study was to evaluate which VA characteristics predicted CMR abnormalities.Methods and ResultsWe enrolled 251 consecutive competitive athletes (74% males, median age 25 [17‐39] years) who underwent CMR for evaluation of VA. We included athletes with >100 premature ventricular beats/24 h or ≥1 repetitive VA (couplets, triplets, or nonsustained ventricular tachycardia) on 12‐lead 24‐hour ambulatory ECG monitoring and negative family history, ECG, and echocardiogram. Features of VA that were evaluated included number, morphology, repetitivity, and response to exercise testing. Left‐ventricular late gadolinium‐enhancement was documented by CMR in 28 (11%) athletes, mostly (n=25) with a subepicardial/midmyocardial stria pattern. On 24‐hour ECG monitoring, premature ventricular beats with multiple morphologies or with right‐bundle‐branch‐block and intermediate/superior axis configuration were documented in 25 (89%) athletes with versus 58 (26%) without late gadolinium‐enhancement (PPP=0.002), (PConclusionsIn athletes with apparently idiopathic VA, simple characteristics such as number and morphology of premature ventricular beats on 12‐lead 24‐hour ambulatory ECG monitoring and response to exercise testing predicted the presence of concealed myocardial abnormalities on CMR. These findings may help cost‐effective CMR prescription.

Background pacemaker induced cardiomyopathy or transient impairment of the left ventricle (LV) function could be common collateral effects of the prolonged right ventricle (RV) pacing in patients with a pacemaker (PM) and pre-existing intra-ventricular conduction disturbances. However, the impact of RV pacing-site on RV performance of patients with right bundle branch block(RBBB) is still under-investigated. Purpose to study the effects of RV pacing in the mid-septal versus apical site on the morpho-functional performance of RV in patients undergoing permanent PM implantation. Methods We prospectively enrolled consecutive patients with a pre-existent complete RBBB and undergoing dual-chamber PM implantation in our institution. We randomized the patients 1:1 to receive the RV catheter fixed either in the apex or in the mid-septal position. Patients with LV systolic dysfunction (LVEF Results a total of 22 patients were randomized in the study, 11 (50%) received RV catheter positioned in the apex and 11 (50%) in the mid-septum, respectively. No baseline differences were recorded between the two groups in clinical characteristics, ECG and echocardiographic parameters. At 2 months follow up, there were no statistically significant difference in the % of RV pacing between the two groups. Nonetheless, RV mid-septal group showed significantly shorter duration of the stimulated QRS (146 ± 12 msec vs. 161 ± 20 msec, p = 0.05), significantly reductions in the RV dimensions (pre: 42 ± 8 mm vs. post: 37 ± 7 mm, p = 0.05) telediastolic area (pre: 12 ± 3 cm2/m2 vs post: 9 ± 4 cm2/ m2, p = 0.02) telediastolic volume (pre: 55 ± 16 ml/m2 vs post: 50 ± 17 ml/m2, p = 0.02) and a significant improvement of RV ejection fraction (pre: 54 ± 9% vs post: 57 ± 11%, p = 0.02) than patients in the RV-apical group. Moreover, patients in the RV-apical group showed significant lowering in the GLS of the LV (pre: -16 ± 3% vs post: -11.7 ± 3%, p Conclusions In this study, mid-septal pacing seems associated with a better morpho-functional RV performance than apical pacing in patients with pre-existent RBBB undergoing permanent PM implantation.

Sudden cardiac death (SCD) of young athletes is an unexpected and tragic event that could occur during sport activities and is frequently related to ventricular arrhythmias. Identifying athletes at risk of SCD remains a major challenge. While specific characteristics of premature ventricular contractions are considered common and benign, other "uncommon" features should require more accurate investigations, in order to determine eligibility for competitive sports. The most common type of idiopathic premature ventricular contractions originates from ventricular outflow tract and is characterized by an ECG pattern with left bundle branch block and inferior QRS axis (infundibular pattern). Another pattern associated with a good prognosis is the "fascicular" morphology, characterized by a typical right bundle branch block, superior QRS axis morphology and QRS duration

Right bundle branch block is relatively frequent in the general population and is generally considered benign in healthy individuals. However, it has been associated with increased cardiovascular risk and all-cause mortality in various cohort studies. Indeed, the presence of right bundle branch block in subjects affected by cardiomyopathies or channelopathies is not rare and may conceal underlying electrocardiographic changes, thus making the diagnosis of such conditions more challenging. The purpose of this review is to analyze the prevalence and clinical significance of right bundle branch block in subjects affected by Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy.

Aims To define the clinical characteristics and long-term clinical outcomes of a large cohort of patients with idiopathic ventricular fibrillation (IVF) and normal 12-lead electrocardiograms (ECGs). Methods and results Patients with ventricular fibrillation as the presenting rhythm, normal baseline, and follow-up ECGs with no signs of cardiac channelopathy including early repolarization or atrioventricular conduction abnormalities, and without structural heart disease were included in a registry. A total of 245 patients (median age: 38 years; males 59%) were recruited from 25 centres. An implantable cardioverter-defibrillator (ICD) was implanted in 226 patients (92%), while 18 patients (8%) were treated with drug therapy only. Over a median follow-up of 63 months (interquartile range: 25–110 months), 12 patients died (5%); in four of them (1.6%) the lethal event was of cardiac origin. Patients treated with antiarrhythmic drugs only had a higher rate of cardiovascular death compared to patients who received an ICD (16% vs. 0.4%, P = 0.001). Fifty-two patients (21%) experienced an arrhythmic recurrence. Age ≤16 years at the time of the first ventricular arrhythmia was the only predictor of arrhythmic recurrence on multivariable analysis [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.18–0.92; P = 0.03]. Conclusion Patients with IVF and persistently normal ECGs frequently have arrhythmic recurrences, but a good prognosis when treated with an ICD. Children are a category of IVF patients at higher risk of arrhythmic recurrences.

Sacubitril/valsartan has been shown to improve clinical outcomes in patients with heart failure and reduced ejection fraction (HFrEF), but its effects on left ventricular (LV) systolic function and reverse remodeling parameters remain to be established. We hereby describe the case of a 41 year old man with HFrEF and severe reduction of left ventricular ejection fraction (LVEF). The patient was first treated with triple HF therapy (beta-blocker, angiotensin converting enzyme inhibitor and mineralocorticoid antagonist), but after three months he was still symptomatic and with an LVEF firmly low. In consideration of poor response to therapy, we switched angiotensin converting enzyme inhibitor to sacubitril/valsartan to the maximum tolerated dose (49/51 mg bid) with a marked improvement in LV systolic function and reduction in LV volumes at follow-up. In light of the almost normalized LVEF the patient was also removed from the list for the implantation of a cardiac resynchronization therapy defibrillator. In conclusion, our case showed a strong beneficial effect of sacubitril/valsartan on reverse remodeling and LVEF beyond the benefits of concomitant optimal medical therapy. This result is particular noteworthy because it was obtained although the patient wasn't able to reach the full dose of the drug. Physicians should always consider this drug effect when more demanding therapeutic strategies are needed for their HF patients.

Background: Idiopathic ventricular fibrillation (IVF) in patients with normal baseline electrocardiograms (ECGs) is a rare disease. Little information is available on the clinical features and long-term follow-up of out-of-hospital cardiac arrest (OHCA) survivors presenting with "true" IVF and 12-lead ECGs that remain normal over time. Objective: To define the clinical and ECG characteristics, as well as long-term clinical outcomes of a large cohort of survivors of OHCA due to "true" IVF. Methods: OHCA survivors with VF as the presenting rhythm, normal baseline and follow-up ECGs with no signs of cardiac channelopathy including early repolarization or atrioventricular (AV) conduction abnormalities, and without structural heart disease were included in a registry. Results: A total of 245 OHCA survivors with IVF (median age: 38 years; males 59%) were recruited from 25 centres. All had normal baseline and follow-up ECGs, and no evidence of structural heart disease. An implantable cardioverter-defibrillator (ICD) was implanted in 226 patients (92%), while 18 patients (8%) were treated with drug therapy only. Over a median follow-up of 63 months (interquartile range: 25-110 months), 12 patients died (5%); in 4 of them (1.6%) the lethal event was of cardiac origin. Patients treated with antiarrhythmic drugs (AADs) only had a higher rate of cardiovascular death compared to patients who received an ICD (16% vs. 0.4%, p=0.001). The ECG and echocardiogram of all patients remained unchanged over time. Fifty-two patients (21%) experienced an arrhythmic recurrence. Age ≤ 16 years at the time of the first ventricular arrhythmia was the only predictor of arrhythmic recurrence on multivariable analysis (HR 0.41, 95% CI 0.18-0.92, p=0.03). Discussion: OHCA survivors of "true" IVF with normal baseline and follow-up ECGs frequently have arrhythmic recurrences, but a good prognosis when treated with an ICD. Children are a category of IVF patients at higher risk of arrhythmic recurrences. Funding: The study was supported by a grant of the Swiss Heart Foundation. Declaration of Interest: G.C. has received a research grant from the Swiss National Foundation. P.L. has received speaker fees and research grants from Boston Scientific, Abbott and Medtronic Research support from UCLH Biomedicine NIHR. F.L. is consultant and has received research support from Medtronic Plc, Abbott, Boston Scientific and Microport. S.B. has received speaker’s bureau from Medtronic and Microport. C.P. has received research grant from Biotronik and Biosense Webster. P.B. is consultant for Biotronik. A.A. is consultant to Abbott, Biosense Webster, Daiichi-Sankyo, Boston Scientific, Medtronic, Microport-CRM; and has received speaker fee from Daiichi-Sankyo, Boston Scientific, Medtronic, Microport-CRM Ethics Approval Statement: Data were collected in accordance with regulations set by the local Institutional Ethics Committee and/or Institutional Review Board.

Background: Risk stratification in asymptomatic patients remains by far the most important yet unresolved clinical problem in the Brugada syndrome (BrS).Objectives: This study sought to ana...

Objective T wave inversion (TWI) has been associated with cardiomyopathies. The hypothesis of this study was that TWI has relevant clinical significance in peri-pubertal athletes. Methods Consecutive male soccer players, aged 8–18 years, undergoing preparticipation screening between January 2008 and March 2009 were enrolled. Medical and family histories were collected; physical examinations, 12-lead ECGs and transthoracic echocardiogram (TTE) were performed. TWI was categorised by ECG lead (anterior (V1–V3), extended anterior (V1–V4), inferior (DII–aVF) and infero-lateral (DII–aVF/V4–V6/DI-aVL)) and by age. Results Overall, 2261 (mean age 12.4 years, 100% Caucasian) athletes were enrolled. TWI in ≥2 consecutive ECG leads was found in 136 athletes (6.0%), mostly in anterior leads (126/136, 92.6%). TWI in anterior leads was associated with TTE abnormalities in 6/126 (4.8%) athletes. TWI in extended anterior (2/136, 1.5%) and inferior (3/136, 2.2%) leads was never associated with abnormal TTE. TWI in infero-lateral leads (5/136, 3.7%) was associated with significant TTE abnormalities (3/5, 60.0%), including one hypertrophic cardiomyopathy (HCM) and two LV hypertrophies. Athletes with normal T waves had TTE abnormalities in 4.4% of cases, including one HCM with deep Q waves in infero-lateral leads. Conclusions In this broad population of peri-pubertal male athletes, TWI in anterior leads was associated with mild cardiac disease in 4.8% of cases, while TWI in infero-lateral leads revealed HCM and LV hypertrophy in 60% of cases. ECG identified all cases of HCM.

In the past years, in vitro and animal studies have demonstrated several direct and indirect anti-arrhythmic effects of n-3 polyunsaturated fatty acids (n-3 PUFAs), at least in part mediated by anti-oxidant, anti-inflammatory and antifibrotic properties. Several epidemiological and clinical studies have been conducted to investigate the eventual benefits of fish oils in the prevention of cardiovascular diseases. The aim of this paper is to critically review current evidence on the anti-arrhythmic effects of n-3 PUFAs in the prevention of sudden cardiac death (SCD) and atrial fibrillation (AF). Published data are conflicting, but some benefits have been reported in the prevention of SCD after myocardial infarction and of AF, generally after long-course administration.

Background Many patients fail to receive β-blockers before cardiac resynchronization therapy defibrillator (CRT-D) implantation, or receive them at a suboptimal dose, and require optimization after implantation. We assessed the effectiveness of a structured program for β-blocker titration in CRT-D patients followed up by means of conventional in-clinic visits or remote monitoring. Methods and results 130 patients undergoing CRT implantation and treated according to the standard practice of the centers were included as a control group. A second group of 124 CRT-D candidates (Study Group) underwent up-titration visits every 2 weeks after implantation (target dose: 10 mg/day of bisoprolol or 50 mg/day of carvedilol). In the Study Group, remote monitoring was undertaken in 66 patients, who received additional equipment for daily transmission of weight and blood pressure data, and scheduled titration telephone calls. In the Control Group, the maximal dose of β-blockers was being administered to 12 (9%) patients on implantation and 21 (16%) on 6-month follow-up examination (p > 0.05). In the Study Group, 25 (20%) patients were receiving the maximal dose of β-blockers on implantation and 72 (58%) on follow-up examination (p < 0.001). The 66 Study Group patients on remote monitoring underwent fewer in-clinic visits (p = 0.034). Of these, 50 (76%) were on the maximal dose after remote up-titration (versus 38% of patients followed up conventionally, p < 0.001). The decrease in left ventricular end-systolic volume was larger in the Study Group (p = 0.040). Conclusions The program for β-blocker up-titration increased the number of patients reaching the target dose and improved the response to the therapy. The use of remote monitoring and daily transfer of weight and blood pressure data facilitated β-blocker titration.

Anti-arrhythmic properties of n-3 polyunsaturated fatty acids, at least in part mediated by anti-oxidant, anti-inflammatory and anti-fibrotic power, have been widely proved. Effect of fish oil on atrial fibrillation, both in primary and in secondary prevention and after cardiac surgery, are controversial, mostly due to lack of homogeneity between studies but also due to individual variability in response to fatty acids administration. Inclusion of measurement of incorporation of fish oil into cell membranes, appears to be essential in future studies, to assess their antiarrhythmic effect.

Background. Exercise causes enhanced sympathetic discharge and results in physiologic tachycardia. However, in some patients with a diseased conduction system resulting from acute ischemia, exercise can precipitate heart block. Methods and results. In this report we describe a 51 years old male patient with transient advanced degree atrioventricular (AV) block developed during recovery from exercise stress testing, resolved after the administration of atropine. Nuclear perfusion imaging demostrated stress-induced ischemia of the inferior-apical segments, and recovery of perfusion in the images obtained at rest. Coronarography showed critical stenosis of the right coronary artery, which was treated by percutaneous coronary intervention (PCI) and drug eluting stent (DES) deployment. Conclusion. Nuclear myocardial perfusion imaging provides noninvasive evidence that transient ischemia of the infero- apical segment can result in advanced degree AV block in patient with critical severe right coronary disease.

A 65-year-old man was referred for atrial fibrillation ablation to our center. Routine pre-procedure transthoracic and transoesophageal echocardiography and cardiac computed tomography examinations showed a normal interatrial septum and fossa ovalis anatomy. Access to left atrium was initially planned using a conventional transseptal needle puncture. During the procedure, several consecutive attempts in conjunction with intracardiac echocardiography support, failed to cross the septum. The procedure was then successfully carried out using a specifically designed radiofrequency transseptal catheter.

Risk stratification in asymptomatic patients remains by far the most important yet unresolved clinical problem in the Brugada syndrome (BrS).This study sought to analyze the usefulness of electrocardiographic parameters as markers of sudden cardiac death (SCD) in BrS.This study analyzed data from 347 consecutive patients (78.4% male; mean age 45 ± 13.1 years) with spontaneous type 1 BrS by ECG parameters but with no history of cardiac arrest (including 91.1% asymptomatic at presentation, 5.2% with a history of atrial fibrillation [AF], and 4% with a history of arrhythmic syncope). Electrocardiographic characteristics at the first clinic visit were analyzed to predict ventricular fibrillation (VF)/SCD during follow-up.During the follow-up (48 ± 38 months), 276 (79.5%) patients remained asymptomatic, 39 (11.2%) developed syncope, and 32 (9.2%) developed VF/SCD. Patients who developed VF/SCD had a lower prevalence of SCN5A gene mutations (p = 0.009) and a higher prevalence of positive electrophysiological study results (p0.0001), a family history of SCD (p = 0.03), and AF (p0.0001). The most powerful marker for VF/SCD was a significant S-wave (≥0.1 mV and/or ≥40 ms) in lead I. In the multivariate analysis, the duration of S-wave in lead I ≥40 ms (hazard ratio: 39.1) and AF (hazard ratio: 3.7) were independent predictors of VF/SCD during follow-up. Electroanatomic mapping in 12 patients showed an endocardial activation time significantly longer in patients with an S-wave in lead I, mostly because of a significant delay in the anterolateral right ventricular outflow tract.The presence of a wide and/or large S-wave in lead I was a powerful predictor of life-threatening ventricular arrhythmias in patients with BrS and no history of cardiac arrest at presentation. However, the prognostic value of a significant S-wave in lead I should be confirmed by larger studies and by an independent confirmation cohort of healthy subjects.

Small single-center comparative studies suggest improved outcomes in cardiac resynchronization therapy (CRT) patients implanted with a quadripolar left ventricular (LV) lead in comparison with non-quadripolar (bipolar) leads. This study represents the first large multicenter prospective registry comparing implant and 6-month postoperative lead performance following CRT-defibrillator (CRT-D) implantation with quadripolar vs. bipolar leads.During a 39-month period, 418 consecutive patients having CRT-D implantation attempts with either a quadripolar (n = 230) or bipolar LV lead (n = 188) were enrolled in the registry. The primary outcome of the study was LV lead failure defined as any abnormality, excluding infection, resulting in surgical lead revision or CRT termination. Additionally, operative and follow-up data were analyzed for significant difference between groups.Baseline characteristics of both groups were similar. In 72.9 % of quadripolar leads versus 65.0 % of bipolar leads, the LV lead successfully engaged the predefined ideal target side branch (p = 0.47). Implant duration and fluoroscopy times were significantly shorter when a quadripolar lead was used (p = 0.007 and p = 0.001, respectively). The primary end point occurred in six patients (2.7 %) in the quadripolar group and in 14 patients (8.0 %) in the bipolar group (p = 0.02). Clinically significant phrenic nerve stimulation (PNS) occurred in 4.6 vs. 14.2 % of quadripolar vs. bipolar patients, respectively (p = 0.002); all PNS were resolved noninvasively through programming in the quadripolar group vs. 84 % in bipolar group (p = 0.75). The use of a bipolar lead was associated with a higher risk of surgical LV lead revision (6.3 vs. 2.3 %; p = 0.057) and a higher incidence of dislodgment (5.7 vs. 2.7 %; p = 0.16).This multicenter study demonstrates that the use of a quadripolar LV lead results in significantly lower rates of lead-related problems and reduced procedural and fluoroscopic times for biventricular system implantation. This has important implications for LV pacing lead choice.