Life-threatening Arrhythmias In Patients Research Articles

Late life-threatening arrhythmia in patients with Brugada syndrome: Results from long-term follow-up in a large Japanese cohort.

Most patients with Brugada syndrome (BrS) are first diagnosed in their 40s, with sudden cardiac death (SCD) often occurring in their 50s. Ventricular fibrillation (VF) may occur in some patients with BrS despite having been asymptomatic for a long period. This study aimed to assess the incidence and risk factors for late life-threatening arrhythmias in patients with BrS. Patients with BrS (n = 523; mean age, 51 ± 13 years; male, n = 497) were enrolled. The risk of late life-threatening arrhythmia was investigated in 225 patients who had experienced no cardiac events (CEs: SCD or ventricular tachyarrhythmia) for at least 10 years after study enrollment. The incidence of CEs during the follow-up period was examined. During the follow-up of the 523 patients, 59 (11%) experienced CEs. The annual incidences of CEs were 2.87%, 0.77%, and 0.09% from study enrollment to 3, 3-10, and after 10 years, respectively. Among 225 patients who had experienced no CEs for at least 10 years after enrollment, fourpatients (1.8%) subsequently experienced CEs. Kaplan-Meier analysis revealed significant differences in the incidence of late CEs between patients with and without a history of symptoms (p = .032). The positive and negative predictive values of late CEs for the programmed electrical stimulation (PES) test were 2.9% and 100%, respectively. Our results suggest that patients with BrS who are asymptomatic and have no ventricular tachycardia/VF inducibility by PES are at extremely low risk of experiencing late life-threatening arrhythmias.

Long-term clinical outcomes of patients with drug-induced type 1 Brugada electrocardiographic pattern: A nationwide cohort registry study

BackgroundThere are limited real-world data on the extended prognosis of patients with drug-induced type 1 Brugada electrocardiogram (ECG). ObjectiveWe assessed the clinical outcomes and predictors of life-threatening arrhythmias in patients with drug-induced type 1 Brugada ECG. MethodsThis multicenter retrospective study, conducted at 21 Italian and Swiss hospitals from July 1997 to May 2021, included consecutive patients with drug-induced type 1 ECG. The primary outcome, a composite of appropriate ICD therapies and sudden cardiac death, was assessed along with the clinical predictors of these events. ResultsA total of 606 patients (mean age 49.7 ± 14.7 years; 423 [69.8%] men) were followed for a median of 60.3 months (interquartile range 23.0–122.4 months). Nineteen patients (3.1%) experienced life-threatening arrhythmias, with a median annual event rate of 0.5% over 5 years and 0.25% over 10 years. The SCN5A mutation was the only predictor of the primary outcome (hazard ratio 4.54; P = .002), whereas a trend was observed for unexplained syncope (hazard ratio 3.85; P = .05). In patients who were asymptomatic at presentation, the median annual rate of life-threatening arrhythmias is 0.24% over 5 years and increases to 1.2% if they have inducible ventricular fibrillation during programmed ventricular stimulation. ConclusionIn patients with drug-induced type 1 Brugada ECG, the annual risk of life-threatening arrhythmias is low, with the SCN5A mutation as the only independent predictor. Unexplained syncope correlated with worse clinical outcomes. Ventricular fibrillation inducibility at programmed ventricular stimulation significantly increases the median annual rate of life-threatening arrhythmias from 0.24% to 1.2% over 5 years.

Associations between Oral Glucose-Lowering Agents and Increased Risk for Life-Threatening Arrhythmias in Patients with Type 2 Diabetes Mellitus-A Literature Review.

Background and Objectives: The relationship between type 2 diabetes mellitus (T2DM) and cardiovascular (CV) morbidity and mortality is well-established. Ventricular arrhythmias (VA) are frequently diagnosed in patients with T2DM, especially in those with associated coronary syndrome, non-ischemic dilated cardiomyopathy (NIDCM), and heart failure (HF). In these patients, VA and sudden cardiac arrest (SCA) are considered responsible for more than 50% of CV deaths. Newly developed glucose-lowering agents (GLA) seem not only to ameliorate CV morbidity and mortality, but also to reduce the risk of VA and SCA. Materials and Methods: We researched the medical literature on Pub-Med, Clarivate, and Google Scholar for original articles published in the last five years that debated the possible effects of various GLA on ventricular arrhythmias. Results: We identified nineteen original articles, nine of them debating the antiarrhythmic effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i); Conclusions: The results concerning the impact of various GLA on VA/SCA were heterogeneous depending on the pharmacological class studied, with some of them having neutral, positive, or negative effects. Although it appears that SGLT2i reduces the prevalence of atrial fibrillation and SCA, their effect on VA is not conclusive.

PO-01-178 MAPPING OF PATHOGENIC VARIANT HOTSPOTS ON THE STRUCTURE OF RYANODINE RECEPTOR TYPE 2 DRIVES A RATIONAL DRUG DESIGN APPROACH FOR CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA

Heritable mutations in RYR2 cause sudden-death predisposing arrhythmia syndromes, such as catecholaminergic polymorphic ventricular tachycardia (CPVT), through increased sarcoplasmic reticulum (SR) diastolic Ca2+ leak. RYR2-encoded ryanodine receptor 2 is an intracellular transmembrane Ca2+ release channel in the SR of cardiomyocytes. Even on optimal medical therapy, breakthrough life-threatening arrhythmias in patients with CPVT are common. We sought to correlate identified pathogenic hotspots with key functional domains on the 3D structure of RyR2 and possible mobile binding sites to determine small molecule targets for reducing SR Ca2+ leak. We performed “signal” to “noise” (S:N) analysis in RYR2 to establish pathogenic hotspots. The minor allele frequency (MAF) of literature-derived disease-associated genetic variants at a given amino acid locus was normalized to the MAF of rare population-based variants in Genome Aggregation Database (gnomAD). Using PyMOL, a heat map overlay was generated using S:N levels and possible molecular binding pockets were identified using software PyMOL and Maestro. The highest cumulative S:N intensity of pathogenic hotspots of each domain localized on the channel domain (28.2%), helical domain 1 (25.6%), central domain (17.7%), and N-terminal domain (16.5%) of RyR2. The SPRY1 (0.498%), P1 (0.147%), handle domain (2.32%), and central U motif (8.88%) had lower S:N. Cumulative S:N intensities were nonexistent for SPRY2, SPRY3, P2, and helical domain 2. Putative small molecule binding pockets were identified in all domains while the largest number localized to the channel domain. Once binding pockets were combined with the heat map structure of RyR2, activator binding pockets of low S:N threshold in the open state of RyR2 were shown to be located heavily on the P2 domain, where CaMKII and PKA binds. The highest S:N intensity was in the channel domain with high S:N levels in other proximal domains localizing near the SR transmembrane in the lumen. Mobile binding pockets between the open and closed state of RyR2 with low S:N intensity may be alternative areas for drug targeting, especially on domains that contain binding pockets for activators of RYR2.

Cardiac-targeted PIASy gene silencing mediates deSUMOylation of caveolin-3 and prevents ischemia/reperfusion-induced Nav1.5 downregulation and ventricular arrhythmias

BackgroundAbnormal myocardial Nav1.5 expression and function cause lethal ventricular arrhythmias during myocardial ischemia–reperfusion (I/R). Protein inhibitor of activated STAT Y (PIASy)-mediated caveolin-3 (Cav-3) SUMO modification affects Cav-3 binding to the voltage-gated sodium channel 1.5 (Nav1.5). PIASy activity is increased after myocardial I/R, but it is unclear whether this is attributable to plasma membrane Nav1.5 downregulation and ventricular arrhythmias.MethodsUsing recombinant adeno-associated virus subtype 9 (AAV9), rat cardiac PIASy was silenced using intraventricular injection of PIASy short hairpin RNA (shRNA). After two weeks, rat hearts were subjected to I/R and electrocardiography was performed to assess malignant arrhythmias. Tissues from peri-infarct areas of the left ventricle were collected for molecular biological measurements.ResultsPIASy was upregulated by I/R (P < 0.01), with increased SUMO2/3 modification of Cav-3 and reduced membrane Nav1.5 density (P < 0.01). AAV9-PIASy shRNA intraventricular injection into the rat heart downregulated PIASy after I/R, at both mRNA and protein levels (P < 0.05 vs. Scramble-shRNA + I/R group), decreased SUMO-modified Cav-3 levels, enhanced Cav-3 binding to Nav1.5, and prevented I/R-induced decrease of Nav1.5 and Cav-3 co-localization in the intercalated disc and lateral membrane. PIASy silencing in rat hearts reduced I/R-induced fatal arrhythmias, which was reflected by a modest decrease in the duration of ventricular fibrillation (VF; P < 0.05 vs. Scramble-shRNA + I/R group) and a significantly reduced arrhythmia score (P < 0.01 vs. Scramble-shRNA + I/R group). The anti-arrhythmic effects of PIASy silencing were also evidenced by decreased episodes of ventricular tachycardia (VT), sustained VT and VF, especially at the time 5–10 min after ischemia (P < 0.05 vs. Scramble-shRNA + IR group). Using in vitro human embryonic kidney 293 T (HEK293T) cells and isolated adult rat cardiomyocyte models exposed to hypoxia/reoxygenation (H/R), we confirmed that increased PIASy promoted Cav-3 modification by SUMO2/3 and Nav1.5/Cav-3 dissociation after H/R. Mutation of SUMO consensus lysine sites in Cav-3 (K38R or K144R) altered the membrane expression levels of Nav1.5 and Cav-3 before and after H/R in HEK293T cells.ConclusionsI/R-induced cardiac PIASy activation increased Cav-3 SUMOylation by SUMO2/3 and dysregulated Nav1.5-related ventricular arrhythmias. Cardiac-targeted PIASy silencing mediated Cav-3 deSUMOylation and partially prevented I/R-induced Nav1.5 downregulation in the plasma membrane of cardiomyocytes, and subsequent ventricular arrhythmias in rats. PIASy was identified as a potential therapeutic target for life-threatening arrhythmias in patients with ischemic heart diseases.

Late gadolinium enhancement is a strong predictor of life threatening arrhythmias in patients with dilated cardiomyopathy undergoing ICD implantation for primary prevention of sudden cardiac death

Abstract Background The usefulness of implantable cardioverter defibrillators (ICD) for primary prevention of arrhythmic sudden cardiac death (SCD) in patients with non-ischemic dilated cardiomyopathy (DCM) has been questioned. Efforts to improve risk stratification have included scores such as the “MADIT-ICD benefit score”, and the use of late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR). The purpose of this study was to evaluate the potential usefulness of these two tools to assess the risk of life-threatening arrhythmias in patients with non-ischemic DCM undergoing ICD implantation for primary prevention of SCD. Methods We conducted a single-center retrospective study of consecutive patients who underwent contrast-enhanced CMR before ICD implantation for primary prevention of SCD. Patients with ischemic cardiomyopathy were used as reference. Patients with non-dilated cardiomyopathies were excluded. The arrhythmic component of the MADIT-ICD benefit score (VT/VF score) was calculated for each patient, and considered high if ≥7, as recommended. The primary endpoint was the occurrence of SCD or life-threatening arrhythmias (VF or VT &amp;gt;200 bpm). Follow-up was performed by device interrogation in all patients except those who suffered SCD. Results A total of 151 patients (93 ischemic, mean age 62±13 years, 75% male) with mean left ventricular ejection fraction (LVEF) of 27±8% were included. Overall, 72% (n=67) ischemic and 45% (n=26) non-ischemic patients had scores ≥7 and were considered high-risk. LGE was present in all patients with ischemic cardiomyopathy, and in 76% (n=44) of patients with non-ischemic DCM. During a median follow-up of 21 (8–38) months, 21 patients (13.9%, 11 ischemic and 10 non-ischemic) met the primary endpoint. Overall, the event-free survival of non-ischemic patients was similar to that of ischemic patients (log rank p=0.269). In patients with non-ischemic DCM, there were 7 arrhythmic events (26.9%) in those with MADIT-ICD VT/VF scores ≥7, and 3 events (9.4%) in those with scores &amp;lt;7 (log rank p=0.104). In the same population, there were 10 arrhythmic events (23%) in patients with LGE, but no events in patients without LGE (log rank p=0.036). LVEF was similar in patients with and without arrhythmic events (26±8% vs. 27±7%, p=0.717), and in those with and without LGE (26±7% vs. 28±9%, p=0.342). Conclusion The presence of LGE is a strong predictor of life threatening arrhythmias in patients in non-ischemic DCM undergoing ICD implantation for primary prevention, seemingly outperforming the clinical MADIT-ICD benefit score. Funding Acknowledgement Type of funding sources: None.

Late gadolinium enhancement is a strong predictor of life threatening arrhythmias in patients with non-ischemic dilated cardiomyopathy undergoing ICD implantation for primary prevention of sudden card

Abstract Funding Acknowledgements Type of funding sources: None. Background The usefulness of implantable cardioverter defibrillators (ICD) for primary prevention of arrhythmic sudden cardiac death (SCD) in patients with non-ischemic dilated cardiomyopathy (DCM) has been questioned. Efforts to improve risk stratification have included scores such as the ‘MADIT-ICD benefit score’, and the use of late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR). The purpose of this study was to evaluate the potential usefulness of these two tools to assess the risk of life-threatening arrhythmias in patients with non-ischemic DCM undergoing ICD implantation for primary prevention of SCD. Methods We conducted a single-center retrospective study of consecutive patients who underwent contrast-enhanced CMR before ICD implantation for primary prevention of SCD. Patients with ischemic cardiomyopathy were used as reference. Patients with non-dilated cardiomyopathies were excluded. The arrhythmic component of the MADIT-ICD benefit score (VT/VF score) was calculated for each patient, and considered high if ≥ 7, as recommended. The primary endpoint was the occurrence of SCD or life-threatening arrhythmias (VF or VT &amp;gt;200 bpm). Follow-up was performed by device interrogation in all patients except those who suffered SCD. Results A total of 151 patients (93 ischemic, mean age 62±13 years, 75% male) with mean left ventricular ejection fraction (LVEF) of 27±8% were included. Overall, 72% (n=67) ischemic and 45% (n=26) non-ischemic patients had scores ≥ 7 and were considered high-risk. LGE was present in all patients with ischemic cardiomyopathy, and in 76% (n=44) of patients with non-ischemic DCM. During a median follow-up of 21 (8-38) months, 21 patients (13.9%, 11 ischemic and 10 non-ischemic) met the primary endpoint. Overall, the event-free survival of non-ischemic patients was similar to that of ischemic patients (log rank p=0.269) – Fig 1A. In patients with non-ischemic DCM, there were 7 arrhythmic events (26.9%) in those with MADIT-ICD VT/VF scores ≥7, and 3 events (9.4%) in those with scores &amp;lt;7 (log rank p= 0.104) – Fig 1B. In the same population, there were 10 arrhythmic events (23%) in patients with LGE, but no events in patients without LGE (log rank p=0.036) – Fig 1C. LVEF was similar in patients with and without arrhythmic events (26±8% vs. 27±7%, p=0.717), and in those with and without LGE (26±7% vs. 28±9%, p=0.342). Conclusion The presence of LGE is a strong predictor of life threatening arrhythmias in patients in non-ischemic DCM undergoing ICD implantation for primary prevention, seemingly outperforming the clinical MADIT-ICD benefit score.

PO-693-06 LATE GADOLINIUM ENHANCEMENT IS A STRONG PREDICTOR OF LIFE-THREATENING ARRHYTHMIAS IN PATIENTS WITH NON-ISCHEMIC DILATED CARDIOMYOPATHY UNDERGOING ICD IMPLANTATION FOR PRIMARY PREVENTION OF SUDDEN CARDIAC DEATH

The usefulness of implantable cardioverter defibrillators (ICD) for primary prevention of arrhythmic sudden cardiac death (SCD) in patients with non-ischemic dilated cardiomyopathy (DCM) has been questioned. Efforts to improve risk stratification have included scores such as the ‘MADIT-ICD benefit score’, and the use of late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR). The purpose of this study was to evaluate the potential usefulness of these two tools to assess the risk of life-threatening arrhythmias in patients with DCM undergoing ICD implantation for primary prevention of SCD. We conducted a single-center retrospective study of consecutive patients who underwent CMR before ICD implantation for primary prevention of SCD. Patients with non-dilated cardiomyopathies were excluded.The arrhythmic component of the MADIT-ICD benefit score (VT/VF score) was calculated, and considered high if ≥ 7, as recommended. The primary endpoint was the occurrence of SCD or life-threatening arrhythmias (VF or VT >200 bpm). Follow-up was performed by device interrogation in all patients except those who suffered SCD. A total of 151 patients (93 ischemic, mean age 62±13 years, 75% male) with mean left ventricular ejection fraction (LVEF) of 27±8% were included. LGE was present in all patients with ischemic cardiomyopathy, and in 76% (n=44) of patients with DCM. During a median of 21 (8-38) months, 21 patients (13.9%, 11 ischemic and 10 DCM) met the primary endpoint. The event-free survival of DCM patients was similar to that of ischemic patients (log rank p=0.269) - Fig 1A. In patients with DCM, there were 7 arrhythmic events (26.9%) in those with MADIT-ICD VT/VF scores ≥7, and 3 (9.4%) in those with scores <7 (log rank p= 0.104) - Fig 1B. In the same population, there were 10 arrhythmic events (23%) in patients with LGE, but no events in patients without LGE (log rank p=0.036) - Fig 1C. LVEF was similar in patients with and without arrhythmic events (26±8% vs. 27±7%, p=0.717), and in those with and without LGE (26±7% vs. 28±9%, p=0.342). The presence of LGE is a strong predictor of life-threatening arrhythmias in patients in non-ischemic DCM undergoing ICD implantation for primary prevention, seemingly outperforming the clinical MADIT-ICD benefit score.

Meta-analysis of incidence and outcomes of life-threatening arrhythmias in takotsubo cardiomyopathy

BackgroundTakotsubo cardiomyopathy (TC) or stress-induced cardiomyopathy is a transient heart condition that clinically resembles an acute coronary syndrome. This study aims to assess the incidence of life-threatening arrhythmias in patients with Takotsubo cardiomyopathy and evaluate the outcomes of patients with life-threatening arrhythmias (LTAs) in Takotsubo cardiomyopathy compared with those without LTA. MethodsWe comprehensively searched the PubMed, Google Scholar, and Embase databases from inception to February 2021. The primary aim of the study was to determine the incidence of LTAs in TC patients. Other outcomes of interest were the odds of in-hospital, long-term mortality, and cardiogenic shock (CS) in TC patients with LTAs versus those without LTAs. For all statistical analyses, ReviewManager and MedCalc were used. ResultsEighteen studies were included in this study involving 55,557 participants (2,185 with LTAs and 53,372 without LTAs). The pooled incidence of LTAs in the patients of TC was found to be 6.29% (CI: 4.70–8.08%; I2 = 94.67%). There was a statistically significant increased risk of in-hospital mortality (OR = 4.74; CI: 2.24–10.04; I2 = 77%, p < 0.0001) and cardiogenic shock (OR = 5.60; CI: 3.51–8.95; I2 = 0%, p < 0.00001) in the LTA group versus the non-LTA group. LTA was not associated with long-term mortality (OR = 2.23; CI: 0.94–5.28; I2 = 53%, p = 0.07). ConclusionThe pooled incidence of life-threatening arrhythmias in the patients of TC was found to be 6.29%. In the group of TC patients with LTAs, the odds of in-hospital mortality and CS, was higher than in the TC patients without LTAs.

Performance evaluation of implantable cardioverter-defibrillators with SmartShock technology in patients with inherited arrhythmogenic diseases

BackgroundPatients with inherited arrhythmogenic diseases (IADs) are often prescribed preventative implantable cardioverter-defibrillators (ICDs) to manage their increased sudden cardiac arrest risk. However, it has been suggested that ICDs in IAD patients may come with additional risk. We aimed to leverage the PainFree SmartShock Technology dataset to compare inappropriate therapies, appropriate therapies, mortality, and complications in patients with and without IAD. MethodsThis retrospective analysis included extracted, physician-adjudicated, arrhythmic episodes from ICD devices. The incidence of arrhythmic events was estimated with the Kaplan-Meier method using the log-rank test. Cox proportional hazards regression was used to estimate hazard ratios (HRs) with their 95% confidence intervals (CIs). ResultsOf the 1699 ICD patients, 77 patients (4.5%) had IAD. Incidence of inappropriate shock was similar in both patients with (3.2% at 24 months) and without (3.8% at 24 months) IAD (HR: 0.80, CI: 0.19–3.30, p = 0.76). In a multivariable analysis IAD was not significantly associated with reduced mortality (HR: 0.64, CI: 0.08–4.80, p = 0.66). The rates of complications were numerically lower in patients with IAD vs without (8.8% vs 9.6% at 24 months respectively), but not statistically significant (HR: 0.83, CI: 0.20–3.38, p = 0.79). ConclusionsIAD patients showed a very low annual rate of inappropriate therapy. This suggests that newer algorithms, such as the SST algorithm, are equally good at identifying and treating life-threatening arrhythmias in patients regardless of whether they have IAD.

Incidence of Atrioventricular Blocks and its Association with In-Hospital Mortality and Morbidity in Patients with Coronavirus Disease 2019

BackgroundCardiovascular sequelae of coronavirus disease 2019 (COVID-19) infection have been explored by clinicians and researchers all over the world. ObjectiveThe purpose of this study was to evaluate the incidence of atrioventricular block (AV) in patients hospitalized for COVID-19 and its association between in-hospital morbidity and mortality. MethodsIn-hospital electrocardiograms (ECGs) of 438 patients were compared with their prior or baseline ECGs to ascertain the development of new onset AV block. Patients who developed new AV blocks were then followed at 30 and 90 days post-discharge to check for resolution of AV block. Demographic characteristics, clinical characteristics, and complications during their hospital stay were evaluated. Major complications including respiratory failure requiring oxygen supplementation and mechanical ventilation, sepsis, deep vein thrombosis, elevated troponins, hospital and intensive care unit (ICU) length of stay, as well as death were compared between those who developed new onset AV blocks and those who did not. ResultsBased on our single center study, the incidence of new onset AV blocks among patients admitted for COVID-19 during the study period was 5.5 cases per 100 patients. New onset AV blocks were not associated with longer hospital and ICU length of stay, increased intubation rates, or increased mortality. ConclusionAlthough the development of a new onset AV block is most likely multifactorial and not solely due to COVID-19, it is still important for clinicians to be mindful about the possibility of developing symptomatic bradycardia and life-threatening arrhythmias in patients admitted for COVID-19. This can be achieved by appropriate rhythm monitoring in-patient but the need for a cardiac event monitor upon discharge is unlikely to be necessary. Careful history taking, including family and drug use history is also of great importance as emerging drug therapies for COVID-19 have potential arrhythmogenic effects.

Mutations in the genes encoding cardiac ion channels may contribute in life-threatening arrhythmias in patients with hypertrophic cardiomyopathy

Mutations in the genes encoding cardiac ion channels may contribute in life-threatening arrhythmias in patients with hypertrophic cardiomyopathy

Advanced cardiac imaging in athlete's heart: unravelling the grey zone between physiologic adaptation and pathology.

Over the last decades, interest toward athlete’s heart has progressively increased, leading to improve the knowledge on exercise-induced heart modifications. Sport may act as a trigger for life-threatening arrhythmias in patients with structural or electrical abnormalities, hence requiring to improve the diagnostic capability to differentiate physiological from pathological remodeling. Pathological alterations are often subtle at the initial stages; therefore, the challenge is to promptly identify athletes at risk of sudden cardiac death during the pre-participation screening protocols. Advanced imaging modalities such as coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) can non-invasively depict coronary vessels and provide a deep morpho-functional and structural characterization of the myocardium, in order to rule out pathological life threatening alterations, which may overlap with athletes’ heart remodeling. The purpose of the present narrative review is to provide an overview of most frequent diagnostic challenges, defining the boundaries between athlete's heart remodeling and pathological structural alteration with a focus on the role and importance of CCTA and CMR.

Management of Young Athletes with Asymptomatic Preexcitation-A Review of the Literature.

Introduction: The management of young athletes with asymptomatic preexcitation remains a challenge, regardless of the progress we have made in understanding the basis of condition and developing catheter ablation procedures. The risk of sudden death, however small, yet definite, being the first symptom is determining our approach. The aim of the study was to establish the current state of knowledge regarding the management of young athletes diagnosed with asymptomatic preexcitation, by conducting a literature review. Material and methods: A comprehensive literature review was completed in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was limited to English language publications using the following search terms: “asymptomatic” or “incidental” and “pre-excitation” or “Wolff–Parkinson–White” or “delta wave” and “athlete” or “sport”. The search was supplemented by hand review of the bibliographies of previous relevant systematic reviews. Results: The search resulted in 85 of abstracts, and the manual search of the bibliographies resulted in 24 additional papers. After careful analysis 10 publications were included in the review. In all but one of the presented papers, the authors used non-invasive methods and then either trans-esophageal or invasive EPS as a way to risk stratify asymptomatic patients. Evidence of rapid conduction through the accessory pathway was considered high risk and prompted sport disqualification. In the analysed reports there were combined: 142 episodes of the life-threatening events (LTE)/sudden death (SCD), of which 56 were reported to occur at rest, 61 during activity and no data were available for 25. Conclusions: athletic activity may impose an increased risk of life-threatening arrhythmias in patients with asymptomatic preexcitation; hence, a separate approach could be considered, especially in patients willing to engage in high-intensity, endurance and competitive sports.

Left Atrial Function Using Cardiovascular Magnetic Resonance Imaging Independently Predicts Life-Threatening Arrhythmias in Patients Referred to Receive a Primary Prevention Implantable Cardioverter Defibrillator

BackgroundIn this study we aimed to investigate left atrial (LA) function, measured from routine cine cardiovascular magnetic resonance imaging, to determine its value for the prediction of sudden cardiac death (SCD) or appropriate implantable cardioverter defibrillator (ICD) shock in patients who received primary prevention ICD implantation. MethodsWe studied 203 patients with ischemic or idiopathic nonischemic dilated cardiomyopathy who underwent cardiovascular magnetic resonance imaging before primary prevention ICD implantation. LA volumes were measured at end-diastole and end-systole from 4- and 2-chamber cine images, and LA emptying function (LAEF) calculated. Patients were followed for the primary composite end point of SCD or appropriate ICD shock. ResultsMean age was 61 ± 12 years with a mean left ventricular ejection fraction of 24 ± 7%. The mean LAEF was 27 ± 15% (range, 0.9%-73%). At a median follow-up of 1639 days, 35 patients (17%) experienced the primary composite outcome. LAEF was strongly associated with the primary outcome (P = 0.001); patients with an LAEF ≤ 30% experienced a cumulative event rate of 26.1% vs 5.7% (hazard ratio, 5.5; P < 0.001) in patients above this cutoff. This finding was maintained in multivariable analysis (hazard ratio, 4.7; P = 0.002) and was consistently shown in the ischemic and nonischemic dilated cardiomyopathy subgroups. ConclusionsLAEF is a simple, powerful, and independent predictor of SCD in patients being referred for primary prevention ICD implantation.

Flecainide-Induced Brugada Syndrome in a Patient With Skeletal Muscle Sodium Channelopathy: A Case Report With Critical Therapeutical Implications and Review of the Literature

Skeletal muscle sodium channelopathies are a group of neuromuscular disorders associated with mutations in the SCN4A gene. Because principal sodium channel isoforms expressed in the skeletal muscles and the heart are distinct one from the other, this condition usually spares cardiac functioning. Nonetheless, evidence on a possible link between skeletal muscle and cardiac sodium channelopathies has emerged in recent years. To date, eight patients bearing pathogenetic mutations in the SCN4A gene and manifesting cardiac electrophysiological alterations have been reported in literature. Among these patients, three presented a phenotype compatible with Brugada syndrome. We report the case of a 29-year-old patient affected by non-dystrophic myotonia associated with a p.G1306E mutation in the SCN4A gene, who presented symptoms of syncope and palpitation after the introduction of flecainide as an anti-myotonic agent. ECG and ajmaline challenge were consistent with the diagnosis of Brugada syndrome, leading to the implantation of a cardioverter defibrillator. No mutation in causative genes for Brugada syndrome was detected. Mexiletine treatment reduced myotonia without any cardiac adverse events. This case report highlights the clinical relevance of the recognition of cardiac electrophysiological alterations in skeletal muscle sodium channelopathies. The discovery of a possible pathogenetic linkage between skeletal muscle and cardiac sodium channelopathies may have significant implications in patients' management, also in light of the fact that class 1C anti-arrhythmics are potential triggers for life-threatening arrhythmias in patients with Brugada syndrome.

224Day-to-day Variation of J-wave Predicts Life-Threatening Arrhythmias in Patients with Brugada syndrome

224Day-to-day Variation of J-wave Predicts Life-Threatening Arrhythmias in Patients with Brugada syndrome

ОСОБЕННОСТИ ВАРИАБЕЛЬНОСТИ СЕРДЕЧНОГО РИТМА У ПАЦИЕНТОВ С ПОСТИНФАРКТНЫМ КАРДИОСКЛЕРОЗОМ И У ПАЦИЕНТОВ С ФАКТОРАМИ РИСКА РАЗВИТИЯ СЕРДЕЧНО-СОСУДИСТЫХ ЗАБОЛЕВАНИЙ

Background. The study of ECG measurements is closely related to ventricular ectopy and the analysis of their relationship to autonomic regulation provides the basis for new ways of diagnosis and treatment of risk-stratified markers of sudden cardiac death. The aim of the study was to develop new approaches to prediction and prevention of life-threatening arrhythmias in patients with myocardial infarction and people with high and very high cardiovascular risk by the SCORE scale. Material and methods. We have analyzed the protocols of Holter monitoring of heart rate of patients with coronary heart disease and those with cardiovascular disease risk factors by the SCORE scale. Results and conclusions. We have established, that people with high cardiovascular risk by the SCORE scale have high stress level, and those with very high cardiovascular risk have the same indicators of heart rate variability, as in people with cardiovascular disease.

Day-to-day Variation of J-wave Predicts Life-Threatening Arrhythmias in Patients with Myocardial Infarction

Day-to-day Variation of J-wave Predicts Life-Threatening Arrhythmias in Patients with Myocardial Infarction

Arrhythmogenic Right Ventricular Cardiomyopathy: Clinical Course and Predictors of Arrhythmic Risk

BackgroundArrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death, but its progression over time and predictors of arrhythmias are still being defined. ObjectivesThis study sought to describe the clinical course of ARVC and occurrence of life-threatening arrhythmic events (LAE) and cardiovascular mortality; identify risk factors associated with increased LAE risk; and define the response to therapy. MethodsWe determined the clinical course of 301 consecutive patients with ARVC using the Kaplan-Meier method adjusted to avoid the bias of delayed entry. Predictors of LAE over 5.8 years of follow-up were determined with Cox multivariable analysis. Treatment efficacy was assessed comparing LAE rates during matched time intervals. ResultsA first LAE occurred in 1.5 per 100 person-years between birth and age 20 years, in 4.0 per 100 person-years between ages 21 and 40 years, and in 2.4 per 100 person-years between ages 41 and 60 years. Cumulative probability of a first LAE at follow-up was 14% at 5 years, 23% at 10 years, and 30% at 15 years. Higher risk of LAE was predicted by atrial fibrillation (hazard ratio [HR]: 4.38; p = 0.002), syncope (HR: 3.36; p < 0.001), participation in strenuous exercise after the diagnosis (HR: 2.98; p = 0.028), hemodynamically tolerated sustained monomorphic ventricular tachycardia (HR: 2.19; p = 0.023), and male sex (HR: 2.49; p = 0.012). No difference was observed in the occurrence of LAE before and after treatment with amiodarone, beta-blockers, sotalol, or ablation. A total of 81 patients received an implantable cardioverter-defibrillator, 34 were successfully defibrillated. ConclusionsThe high risk of life-threatening arrhythmias in patients with ARVC spans from adolescence to advanced age, reaching its peak between ages 21 and 40 years. Atrial fibrillation, syncope, participation in strenuous exercise after the diagnosis of ARVC, hemodynamically tolerated sustained monomorphic ventricular tachycardia, and male sex predicted lethal arrhythmias at follow-up. The lack of efficacy of antiarrhythmic therapy and the life-saving role of the implantable cardioverter-defibrillator highlight the importance of risk stratification for patient management.