Sudden Arrhythmic Death Research Articles

Predicting arrhythmias in primary prevention heart failure patients: picking up the fragments

Identifying patients with high-risk heart failure (HF) who would benefit from an implantable cardioverter-defibrillator (ICD) remains controversial. A potential marker for arrhythmic sudden death is fragmented QRS (fQRS). fQRS is...

Sudden cardiac death related to physical exercise in the young: a nationwide cohort study of Australia.

Sudden cardiac death (SCD) during physical exercise is devastating. To evaluate causes and circumstances of exercise-related SCD in the young in Australia. We reviewed the National Coronial Information System database for deaths in Australia relating to cardiovascular disease in cases aged 10-35 years between 2000 and 2016. Cases who had undertaken physical exercise at the time of the event were included. We collected demographics, circumstances of death, type of physical exercise, bystander cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use prior to ambulance arrival. Over a 17-year period, 1925 SCD cases were identified, of which 110 (6%) cases (median age 27 years (interquartile range 21-32 years); 92% male) were related to sports/physical exercise. Thirteen (12%) cases occurred in active athletes. Most common causes were coronary artery disease (CAD; 37%) and sudden arrhythmic death syndrome (SADS; 20%). Among Aboriginal and Torres Strait Islanders (n = 10), all deaths were related to CAD. Australian Rules Football (24%), running/jogging (14%) and soccer (14%) were the most frequent physical exercise activities. Prior symptoms were present in 39% (chest pain 37%, pre-syncope/syncope 26%). Most (87%) were witnessed, with bystander CPR in 70%. AED use prior to ambulance arrival was 8%. The present study demonstrates the high occurrence of CAD and SADS in SCD in the young related to physical exercise. Aboriginal and Torres Strait Islanders were disproportionately affected by CAD. Although events were commonly witnessed, AED was seldom used prior to ambulance arrival and highlights an important opportunity to improve outcomes in the post-arrest chain of survival.

IDENTIFICATION OF ARRHYTHMIAS PRECEDING VENTRICULAR FIBRILLATION IN PATIENTS PRESCRIBED PHILIPS MOBILE CARDIAC OUTPATIENT TELEMETRY

Ventricular Fibrillation (VF) is a potentially lethal arrhythmia seen on telemetry monitoring. Ambulatory ECG in arrhythmic sudden death has shown VF as the terminal arrhythmia in about 80% of cases. Studies of VF triggers in the ambulatory setting are sparse, but suggest VF is most often due to ventricular tachycardia (VT).

The N-linker region of hERG1a upregulates hERG1b potassium channels

A major physiological role of hERG1 (human Ether-á-go-go-Related Gene 1) potassium channels is to repolarize cardiac action potentials. Two isoforms, hERG1a and hERG1b, associate to form the potassium current IKr in cardiomyocytes. Inherited mutations in hERG1a or hERG1b cause prolonged cardiac repolarization, long QT syndrome, and sudden death arrhythmia. hERG1a subunits assemble with and enhance the number of hERG1b subunits at the plasma membrane, but the mechanism for the increase in hERG1b by hERG1a is not well understood. Here, we report that the hERG1a N-terminal region expressed in trans with hERG1b markedly increased hERG1b currents and increased biotin-labeled hERG1b protein at the membrane surface. hERG1b channels with a deletion of the N-terminal 1b domain did not have a measurable increase in current or biotinylated protein when coexpressed with hERG1a N-terminal regions, indicating that the 1b domain was required for the increase in hERG1b. Using a biochemical pull-down interaction assay and a FRET hybridization experiment, we detected a direct interaction between the hERG1a N-terminal region and the hERG1b N-terminal region. Using engineered deletions and alanine mutagenesis, we identified a short span of amino acids at positions 216 to 220 within the hERG1a “N-linker” region that were necessary for the upregulation of hERG1b. We propose that direct structural interactions between the hERG1a N-linker region and the hERG1b 1b domain increase hERG1b at the plasma membrane. Mechanisms regulating hERG1a and hERG1b are likely critical for cardiac function, may be disrupted by long QT syndrome mutants, and serve as potential targets for therapeutics.

Effects of Mexiletine on a Race-specific Mutation in Nav1.5 Associated With Long QT Syndrome.

The voltage-gated sodium channel Nav1.5 plays an essential role in the generation and propagation of action potential in cardiomyocytes. Mutations in Nav1.5 have been associated with LQT syndrome, Brugada syndrome, and sudden arrhythmia death syndrome. Genetic studies showed that Nav1.5 mutations vary across race-ethnic groups. Here we investigated an Asian-specific mutation Nav1.5-P1090L associated with LQT syndrome. We found that Nav1.5-P1090L mutation perturbed the sodium channel function. It altered the gating process of the channel and exhibited an enhanced window current. Treatment with mexiletine reversed the depolarization shift of the steady-state inactivation produced by P1090L. Mexiletine also modified the recovery from steady-state inactivation and the development of inactivation of P1090L. It rescued the dysfunctional inactivation of P1090L and reduced the P1090L channel’s availability.

Structural and electrophysiological basis for the modulation of KCNQ1 channel currents by ML277

The KCNQ1 ion channel plays critical physiological roles in electrical excitability and K+ recycling in organs including the heart, brain, and gut. Loss of function is relatively common and can cause sudden arrhythmic death, sudden infant death, epilepsy and deafness. Here, we report cryogenic electron microscopic (cryo-EM) structures of Xenopus KCNQ1 bound to Ca2+/Calmodulin, with and without the KCNQ1 channel activator, ML277. A single binding site for ML277 was identified, localized to a pocket lined by the S4-S5 linker, S5 and S6 helices of two separate subunits. Several pocket residues are not conserved in other KCNQ isoforms, explaining specificity. MD simulations and point mutations support this binding location for ML277 in open and closed channels and reveal that prevention of inactivation is an important component of the activator effect. Our work provides direction for therapeutic intervention targeting KCNQ1 loss of function pathologies including long QT interval syndrome and seizures.

A Comparative Study Between Amiodarone and Implantable Cardioverter-Defibrillator in Decreasing Mortality From Sudden Cardiac Death in High-Risk Patients: A Systematic Review and Meta-Analysis.

Sudden cardiac death (SCD) is an unexpected death that occurs within one hour of symptom onset. In the United States, sudden cardiac death is considered the leading cause of natural death, accounting for 325,000 adult patients annually. SCD is more common in adult patients (above the mid-30s) and men. The risk factors that predict SCD are categorized into clinical, sociological, genetic, and psychological. To prevent the occurrence of SCD, several treatment options, especially antiarrhythmic drugs and implantable cardioverter-defibrillator (ICD), have been used.A literature search from 2000 to 2022 was conducted on six electronic databases: PubMed, Cochrane Library, Web of Science, Embase, ScienceDirect, and Google Scholar. The search query used Boolean expressions and keywords such as amiodarone, implantable cardioverter-defibrillator, sudden cardiac death, cardiac arrest, arrhythmic death, and all-cause mortality. The articles identified from the literature search were screened using the eligibility criteria, resulting in eight articles relevant for inclusion in the review. A meta-analysis of data from six of the included studies showed that ICD was more effective in the reduction of SCD rates, with an SCD rate of 5.97% (n = 84/1,408) observed in the ICD group compared with an SCD rate of 11.81% (n = 168/1,423) observed in the amiodarone group. The results also show that ICD was more effective in reducing all-cause mortality compared with amiodarone (odds ratio (OR): 1.36; 95% confidence interval (CI): 1.06-1.74; I2 = 57%; P = 0.03).ICD treatment of high-risk patients was more effective in reducing SCD and all-cause mortality rates compared with amiodarone treatment. There is evidence that amiodarone can be used as an adjuvant treatment option, especially for patients who are not eligible for ICD treatment and those who face more adverse events. Evidence has also shown that using amiodarone with ICD treatment significantly improves survival rates compared to ICD treatment only.

The peri-infarct gray zone of myocardial fibrosis is a better predictor of ventricular arrhythmias than dense core fibrosis in patients with previous myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Background Current sudden cardiac death (SCD) risk stratification relies heavily on left ventricular ejection fraction (LVEF), but markers to refine risk assessment are needed. Dense core fibrosis (DCF) and peri-infarct "gray zone" of myocardial fibrosis (GZF) on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) have been proposed as potential arrhythmogenic substrates. The aim of our study was to determine whether DCF and GZF could predict the occurrence of ventricular arrhythmias in patients with previous myocardial infarction. Methods We performed a single centre retrospective study enrolling consecutive patients with previous myocardial infarction undergoing CMR before implantable cardioverter-defibrillator (ICD) implantation. Areas of LGE were subdivided into "core" DCF and "peri-infarct" GZF zones based on signal intensity (>5 SD, and 2-5 SD above the mean of reference myocardium, respectively). The primary endpoint was a composite of sudden arrhythmic death, appropriate ICD shock, ventricular fibrillation (VF), or sustained ventricular tachycardia (VT) as detected by the device. Results A total of 88 patients (median age 61 years [IQR 54-73], 84% male, median LVEF 30% [IQR 23-36%], 14% secondary prevention) were included. During a median follow-up of 23 months [IQR 9-38], 13 patients reached the primary endpoint (10 appropriate ICD shock, 2 sustained VT or VF, and 1 sudden arrhythmic death). Patients who attained the primary endpoint had similar DCF (30.4g ± 14.7 vs. 28.0g ± 15.3; P = 0.601) but a greater amount of GZF (18.1g ± 9.6 vs. 11.9g ± 6.7; P = 0.005). On univariate analysis, GZF was associated with the composite endpoint (HR: 1.09 per gram; 95%CI: 1.02-1.15; P = 0.006), whereas DCF was not (HR: 1.01 per gram; 95%CI: 0.98-1.05; P = 0.571). After adjustment for LVEF, GZF remained independently associated with the primary endpoint (adjusted HR: 1.06 per gram; 95% CI: 1.01-1.12; P = 0.035). Decision tree analysis identified 11.9g of GZF as the best cut-off to predict life-threatening arrhythmic events. The primary endpoint occurred in 11 out of the 35 patients (31.4%) with GZF ≥11.9g, but in only 2 of the 53 patients (3.8%) with GZF <11.9g – Figure. Conclusions The extent of peri-infarct GZF seems to be a better predictor of ventricular arrhythmias than DCF. This parameter may be useful to identify a subgroup of patients with previous myocardial infarction at increased risk of life-threatening arrhythmic events.

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 >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 <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.

Failed shocks in hypertrophic cardiomyopathy patients: prevalence, predictors and outcome

Abstract Funding Acknowledgements Type of funding sources: None. Introduction An implantable cardioverter-defibrillator (ICD) is used in selected high-risk hypertrophic cardiomyopathy (HCM) patients in order to prevent sudden arrhythmic death. The unique features of this population raise concerns regarding the reliability of successful defibrillation. Purpose To describe the rate and discover potential predictors of failed shocks in HCM patients. Methods We retrospectively evaluated all HCM patients with an ICD from a single tertiary medical center. Clinical, electrocardiographic and echocardiographic data were collected and compared among patients with and without failed shocks. Results A total of 99 patients (77% male, 45±17 years old) were analyzed. Over a median follow up of 6.3 years (IQR 2.6-10.7), 20 patients developed sustained ventricular arrhythmia (VTA). Of those, 18 patients received appropriate shocks from their ICD. VTA was associated with younger age at diagnosis, history of syncope and thicker maximal LV width. Six patients experienced at least one failed shock. The likelihood of failed shocks was similar when single or dual coil electrodes were used (dual coils in 67% of patients with failed shocks and 50% in those without), and the only predictor was increased wall thickness [OR 1.2 (1.07-1.38) per 1 mm]. All-cause mortality was low and similar in patients with an without failed shocks (0% vs 8%, P=0.5) Conclusions Failed shocks are a rare entity in HCM patients. Increased maximal LV width was the only predictor of those events. Our findings support avoiding defibrillation threshold testing routinely, but may indicate its need in patients with extreme LV wall thickening (≥23 mm).

P24 WEAREBLE CARDIOVERTER – DEFIBRILLATOR : UTILITY AND USER FRIENDLINESS

Abstract Background Worldwide, cardiovascular disease are still a major mode of death, being sudden arrhythmic death (SCD)25 % of total death. Implantable cardioverter defibrillator (ICD) is an effective weapon for SCD prevention in high risk patients with reasonable expectation of survival with good functional status for >1 year. However sometimes the risk of SCD can be transient, so the use of a wearable cardioverter defibrillator (WCD) is considered. Methods We considered consecutively 40 patients discharged from our cardiology department of Piacenza and Castel san Giovanni that, for potentially transient high risk of SCD, weared a WCD from August 2017 to September 2021, after a systematic education session lasting 30 – 45 minutes. They are followed through remote monitoring. Results Out of 40 patients, with average age 66 years old and average left ventricular ejection fraction (LVEF) 29%, 88% were males, 70 % suffered from arterial hypertension, 32% diabetes mellitus, 17,5 % peripheral vascular disease, 35 % chronic renal failure, 55% heart failure, 7,5% previous stroke. 56% of these patients weared WCD for severe systolic disfunction in ischemic cardiac disease after recent myocardial infarction, after percutaneous coronary intervention or coronary artery bypass graft, 7% after removal of an infected ICD, 9 % whilst awaiting completion of diagnostic tests (chanalopathies/right arrhythmogenic ventricular cardiomyopathy), 34% after newly diagnosed cardiomyopathy.The patients were discharged in high risk mode of SCD with WCD protection.The average wearing time of WCD was 51 days and 22,98 hours daily. We received 953 trasmissions, with 21 events: 7 ventricular tachicardia, 4 Sopraventricular tachicardia and 5 T wave oversensing .Neither inappropriate shock and neither death were detected .After wearing time and after clinical evaluation, only 52% of patients were subjected to ICD implantation. Conclusions In our experience we may consider that WCD use is effective, safe and with a good adherence in all patients, considering wearing time. The WCD allows saving resources with less hospitalization time.

P175 ELECTROCARDIOGRAPHIC ELEMENTS ASSOCIATED WITH ARRHYTHMIC RISK IN BRUGADA SYNDROME

Abstract Introduction Brugada syndrome is an inherited disease characterized by an increased arrhythmic risk and sudden death. The type 1 ECG pattern is the only standard required to make a diagnosis but the stratification of arrhythmic risk remains a controversial element. Some electrocardiographic signs have been described as associated with an increased arrhythmic risk. We present a case of Brugada Syndrome in which different electrocardiographic elements of incremental risk could have predicted the later evolution of the clinical case. Clinical Case A 68–year–old male patient with family history of sudden cardiac death (brother 51aa) and occasional finding of Brugada type 1 ECG pattern (2009), implanted with Medtronic bicameral ICD device in primary prevention. The electrocardiogram shows type 1 Brugada pattern in the right precordials with characteristic ST–elevation, followed by a concave ST segment, one of the signs of association with an increased arrhythmic risk; first–degree AV block with a long PR (323 msec) associated with the presence of the SCN5A mutation and an increased risk of arrhythmic events and sudden cardiac death; in the end a fragmented QRS in V2 with extended duration (153 ms). At the next follow–up the patient had some episodes of arrhythmic storm, effectively treated by the device; in consideration of the arrhythmic burden, he was subjected to epicardial ablation and was also subjected to genetic analysis that was positive for pathological mutation on the SCN5A gene (SCN5A ex 22: c.3929C>T;p.Pro1310Leu). Conclusions Brugada Syndrome can be diagnosed from the type 1 ECG pattern, but the current risk stratification score remains a controversial element. Electrocardiographic signs of malignancy can contribute to create a multiparametric evaluation of the patient in order to predict future arrhythmic events. Fig 1. ECG: RS 74 bpm, first–degree AV block (PR 323 msec), BFA, Brugada type 1 pattern (QRS 153 ms), fragmented QRS in V2. Fig. 2 Family tree.

C39 ECHOCARDIOGRAPHIC PREDICTORS OF MALIGNANT EVENTS IN ARRHYTHMIC MITRAL VALVE PROLAPSE POPULATION

Abstract Background Bileaflet mitral valve prolapse (bMVP) has been linked to major arrhythmic events and sudden cardiac death (SCD). Solid evidence of consistent predictors of SCD in this setting is still lacking. Echocardiography is the best tool for the analysis of ventricle mechanics and for the correlation with electrical myocardial activation. The aim of this study was to find new predictors of malignant events within an arrhythmic MVP population. Methods We conducted a retrospective comparative analysis, selecting 22 patients with bMVP with a high arrhythmic risk profile. 6 of them had a previous major arrhythmic event (5 aborted SCD, one cardiogenic syncope) and previously received ICD implantation (ICD–MVP), while 16 presented with a high arrhythmic burden without major events (A–MVP). All patients underwent transthoracic echocardiography in the last year. Each echocardiogram followed a specific protocol focused on mitral valve anatomy and ventricular contraction using 2D imaging, 3D imaging, tissue doppler imaging and speckle tracking analysis. Results ICD–MVP group, compared with A–MVP group, presented a longer anterior leaflet (AML) length (28,6 mm, IQR: 24,1–31,1 mm; vs 21,4 mm, IQR: 20,4–24,0 mm; p = 0,03), larger mitral valve annulus (MVA) indexed area (6,88 cm2/m2, IQR 6,27–7,87 cm2/m2 vs 5,44 cm2/m2, IQR: 4,93–6,15 cm2/m2, p = 0,02), lower MVA anteroposterior diameter/AML length ratio (1,24, IQR: 1,21–1,41 vs 1,50, IQR 1,32–1,62; p = 0,049), higher inferolateral basal S3 velocity (26 cm/s, IQR: 20,8–29,6 cm/s vs 14,2 cm/s, IQR 10,1–21,3 cm/s; p = 0,02) and a greater mechanical dispersion (MD) of the basal and mid–ventricular segments calculated with speckle tracking (128 ms, IQR: 125–131 ms; vs 58 ms, IQR 45–106 ms; p = 0,03). Mitral regurgitation grading, instead, did not correlate with malignant events. Best predictors of malignant events were AML length and MD of basal and mid–ventricular segments. Cut–off values with highest sensibility and specificity above 80% were 26 mm for AML length and 122 ms for MD of basal and mid–ventricular segments. Logistic bivariate regression confirmed AML length as an independent predictor of malignant events (p = 0,01), while MD of basal and mid–ventricular segments showed a trend toward significancy (p = 0,07). Conclusion Five parameters were found to be predictors of malignant events in a high–risk MVP population. AML length and MD of the basal and mid–ventricular segments presented the best predictive value.

Ventricular tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy: How to Manage?

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a condition characterized by fibrofatty replacement of the RV myocardium due to genetic abnormality. Structural changes may be absent or minor in the early stages of the disease and be localized in a specific region of the RV. Clinically it appears as RV electrical instability. To reduce the risk of arrhythmic events or sudden cardiac death, device therapy and pharmacotherapy may be recommended. In this paper, we describe a case of a female with ARVC and a brief discussion based on a literature review. The patient presented with chest discomfort accompanied by palpitation. An electrocardiogram (ECG) showed ventricular tachycardia of RV apex origin, and convert to symmetric inverted T-waves and probable epsilon waves in the right precordial leads, mimicking a pseudo-right bundle branch block (RBBB) pattern following electrical cardioversion. The parasternal short-axis view of echocardiography shows severe right ventricular dilatation. Subsequent workup using CMR was planned but the patient refused. We diagnosed this patient with ventricular tachycardia on a background of suspicious arrhythmogenic right ventricular cardiomyopathy. We were able to provide accurate diagnosis and treatment, avoiding potentially fatal consequences. As a result, it is critical to recognize potential ARVC ECG findings and to know when to pursue further research and implement therapies.

BS-512-03 HIGH-RESOLUTION STRUCTURE-FUNCTION MAPPING OF INTACT HEARTS REVEALS ALTERED SYMPATHETIC CONTROL OF INFARCT BORDER ZONES

Intramyocardial sympathetic nerve remodeling after myocardial infarction (MI) contributes to adverse outcomes such as sudden arrhythmic death, yet the underlying structural mechanisms are poorly understood. This is partly due to challenges in directly correlating high-resolution structural and electrical data from the same heart.

BS-400-26 HIGH-RESOLUTION STRUCTURE-FUNCTION MAPPING OF INTACT HEARTS REVEALS ALTERED SYMPATHETIC CONTROL OF INFARCT BORDER ZONES

Intramyocardial sympathetic nerve remodeling after myocardial infarction (MI) contributes to adverse outcomes such as sudden arrhythmic death, yet the underlying structural mechanisms are poorly understood. This is partly due to challenges in directly correlating high-resolution structural and electrical data from the same heart.

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.

PO-626-04 THE PERI-INFARCT “GRAY ZONE” OF MYOCARDIAL FIBROSIS IS A BETTER PREDICTOR OF VENTRICULAR ARRHYTHMIAS THAN DENSE CORE FIBROSIS IN PATIENTS WITH PREVIOUS MYOCARDIAL INFARCTION

Current sudden cardiac death (SCD) risk stratification relies heavily on left ventricular ejection fraction (LVEF), but markers to refine risk assessment are needed. Dense core fibrosis (DCF) and peri-infarct “gray zone” of myocardial fibrosis (GZF) on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) have been proposed as arrhythmogenic substrates. We aimed to determine whether DCF and GZF could predict the occurrence of ventricular arrhythmias in patients with previous myocardial infarction. We performed a single centre retrospective study enrolling consecutive patients with previous myocardial infarction undergoing CMR before implantable cardioverter-defibrillator (ICD) implantation. Areas of LGE were subdivided into “core” DCF and “peri-infarct” GZF zones based on signal intensity (>5 SD, and 2-5 SD above the mean of reference myocardium, respectively). The primary endpoint was a composite of sudden arrhythmic death, appropriate ICD shock, ventricular fibrillation (VF), or sustained ventricular tachycardia (VT) as detected by the device. A total of 88 patients (median age 61 years [IQR 54-73], 84% male, median LVEF 30% [IQR 23-36%]) were included. During a median follow-up of 23 months [IQR 9-38], 13 patients reached the primary endpoint. Patients who attained the primary endpoint had similar DCF (30.4g ± 14.7 vs. 28.0g ± 15.3; P = 0.601) but a greater amount of GZF (18.1g ± 9.6 vs. 11.9g ± 6.7; P = 0.005). On univariate analysis, GZF was associated with the composite endpoint (HR: 1.09 per gram; 95%CI: 1.02-1.15; P=0.006), whereas DCF was not (HR: 1.01 per gram; 95%CI: 0.98-1.05; P=0.571). After adjustment for LVEF, GZF remained independently associated with the primary endpoint (adjusted HR: 1.06 per gram; 95% CI: 1.01-1.12; P=0.035). Decision tree analysis identified 11.9g of GZF as the best cut-off to predict arrhythmic events. The primary endpoint occurred in 11 out of the 35 patients (31.4%) with GZF ≥11.9g, but in only 2 of the 53 patients (3.8%) with GZF <11.9g - Figure. The extent of peri-infarct GZF seems to be a better predictor of ventricular arrhythmias than DCF. This parameter may be useful to identify a subgroup of patients with previous myocardial infarction at increased risk of life-threatening arrhythmic events.

PO-655-07 AUTOMATIC DETECTION OF CONGENITAL LONG QT SYNDROME ON ECG WITH DEEP NEURAL NETWORKS

Congenital long QT syndrome (LQTS) is a channelopathy associated with syncope, polymorphic VT, and rarely sudden arrhythmic death. While often detected by QT prolongation on the resting ECG, 50% of patients have a normal or borderline QT interval, necessitating further investigation (i.e. exercise treadmill and genetic testing). A deep neural network may accurately identify latent LQTS using the resting ECG.

Molecular genetic markers of QT interval duration and sudden cardiac death: literature review

The study of sudden cardiac death (SCD) and its etiopathogenesis in cardiology practice remains one of the most pressing public health problems. In Western countries, SCD accounts for 20% of the total mortality and 50% of mortality associated with cardiovascular diseases. Considering the electrical instability in the myocardium as one of the main reasons for the development of life-threatening arrhythmias (ventricular tachycardia / ventricular fibrillation) and SCD, one should be aware of such provoking factors as ischemic heart disease, myocarditis, valvular heart disease, pharmacological influences, cardiomyopathy, and channelopathy. An increase or decrease in the duration of the QT interval, which reflects the work of ion channels, as well as ventricular depolarization and repolarization, increases the risk of SCD.The aim of this review was to study and analyze the available literature data on the relationship of molecular genetic markers with the duration of the QT interval.Currently, there is a number of genetic studies that allow to identify a large number of mutations and polymorphisms of known genes that affect the variability of the QT interval, showing their significance in risk stratification of sudden arrhythmic death and choosing the right tactics for managing, preventing, and treating patients, thus reducing the risk of SCD. The predictive value of genetic testing is the highest for long QT syndrome (LQTS), for which a gene-specific risk profile has been established, and lower for other channelopathies. A large amount of genetic data may be a promising approach to quantifying the risk of SCD, especially at a young age, which will be facilitated by further study of this problem.