Early Repolarization Research Articles

Abstract 4136839: HBI-3000: Pharmacological Conversion of Atrial Fibrillation With Unique Defense Against Excessive QT Interval Prolongation

Background: HBI-3000 (Sulcardine sulfate) is a new antiarrhythmic drug (AAD) that inhibits multiple cardiac ion channels (INa-peak, INa-late, ICa,L and IKr (hERG)) with uniquely similar potencies. A major AAD limitation is malignant proarrhythmia due to excessive hERG-mediated delay in repolarization, manifested by QT prolongation with proportional J to T peak [JTp] prolongation. While sulcardine inhibits hERG, it also possesses an intrinsic protective mechanism, inhibiting inward INa-late and ICa,L early repolarization currents. In Phase 1 volunteers in sinus rhythm (SR) therapeutic levels of sulcardine not only reduced but reversed the lengthening of the rate-corrected JTp (JTpc), reducing the extent of hERG-related QT prolongation. We investigated this protective JTpc effect in atrial fibrillation (AF) patients at the anticipated clinical dose, and examined the relationships between plasma concentration, QT prolongation, and the JTPc reduction. Methods: Ten patients received 350 mg HBI-3000 IV over 30 min in a Phase 2 open-label study of patients with acute AF. Sulcardine plasma concentrations and ECG intervals (from 5-min summary ECGs) were obtained at baseline and several time points. Mean baseline-subtracted, heart rate-corrected QTcF (dQTcF) and JTp (dJTpc; Johannesen’s method) were calculated at each time point. AF patient data were compared to those of volunteers in SR. Results: In AF patients, dQTcF prolonged with a linear relationship to plasma concentration as expected (Fig 1A, blue). HBI-3000 IV produced a large linear reduction in JTpc contribution to the QT interval (Fig 1A, red). This is consistent with findings in SR (Fig 1B [350 mg dose] and 1C [360 mg dose]) and unique among AADs that inhibit IKr along with INa-late and/or ICa,L. Calculated dQTcF changes without the JTpc effect were greater than the observed dQTcF (Fig 1A, green) by 27%-76% at Cmax in the three studies. Conclusions: HBI-3000 (Sulcardine) exhibits dQTcF prolongation protection in both AF and SR due to a unique pattern of channel fluxes that shortens early repolarization. This shorter dJTp interval acts as a mechanism for effectively limiting excessive QT prolongation and reducing proarrhythmic risk. [Registration: NCT04680026]

ATrial arrhythmias in inhEriTed aRrhythmIa Syndromes: results from the TETRIS study.

Little is known about the distribution and clinical course of patients with inherited arrhythmia syndrome (IAS) and concomitant atrial arrhythmias (AAs). 1) to characterize the distribution of AAs in patients with IAS and 2) evaluate the long-term clinical course of these patients. An international multicenter study was performed and involved 28 centers in 16 countries. Inclusion criteria were: 1) IAS and 2) ECG documentation of AAs. The primary endpoint was a composite of sudden cardiac death, sustained VAs or appropriate ICD interventions. Strokes, inappropriate ICD shocks due to AAs, and the occurrence of sinus node dysfunction were assessed. A total of 522 patients with IAS and AAs were included. Most patients were diagnosed with Brugada syndrome (n=355, 68%) and long-QT syndrome (n=93, 18%). The remaining patients (n=71, 14%) presented with short-QT syndrome, early repolarization syndrome (ERS), catecholaminergic polymorphic ventricular tachycardia (CPVT), progressive cardiac conduction diseases, or idiopathic ventricular fibrillation. Atrial fibrillation (AF) was the most prevalent AA (82%), followed by atrial flutter (9%) and atrial tachycardia (9%). AA was the first clinical manifestation of IAS in 52% of patients. More than one type of AAs was documented in 23% of patients. Nine patients (3%) experienced VA before the diagnosis of IAS, due the use of anti-arrhythmic medications taken for the AA. The incidence of the primary endpoint was 1.4% per year, with a twofold increase observed in patients who experienced their first AA before the age of 20 (OR 2.2, p=0.043). This was consistent across the different forms of IAS. Inappropriate ICD shock due to AAs were reported in 2.8% of patients, strokes in 4.4% and sinus node dysfunction in 9.6%. Among patients with IAS and AAs, AA is the first clinical manifestation in about half of the cases, with more than one form of AAs present in one-fourth of the patients. The occurrence of AA earlier in life may be associated with a higher risk of ventricular arrhythmias. The occurrence of stroke and sinus node dysfunction is not-infrequently in this cohort.

Ion Channel Diseases as a Cause of Sudden Cardiac Death in Young People: Aspects of Their Diagnosis, Treatment, and Pathogenesis.

Sudden cardiac death (SCD) is the death of an apparently healthy person within one hour of the onset of symptoms, or within 24 hours of last being seen alive and well-with no evidence of an extra-cardiac cause. In autopsied cases, SCD is defined as the natural unexpected death of unknown or cardiac cause. The reported incidence figures for SCD vary widely. This review is based on clinical registry studies, meta-analyses, randomized controlled trials, systematic reviews, and current guidelines that were retrieved by a selective search in PubMed employing the key words "channelopathy," "Brugada syndrome," "long QT syndrome," "catecholaminergic polymorphic ventricular tachycardia," "short QT syndrome," and "early repolarization." Approximately 18% of cases of SCD in young persons are associated with cardiac channelopathy. The most common ion channel diseases affecting the heart are long QT syndrome and Brugada syndrome. The diagnosis is established by specific ECG abnormalities in the absence of structural heart disease. These can be unmasked by various maneuvers, e.g., the administration of sodium-channel blockers in Brugada syndrome. Imaging studies such as echocardiography, coronary angiography, and computed tomography are used to rule out structural heart disease and coronary artery disease. Long-term ECG and risk stratification scores can be useful aids to therapeutic decision-making. For some of these diseases, it is advisable for the patient to avoid particular triggers of ECG changes and cardiac arrhythmias in his or her everyday life. The near relatives of persons with congenital ion channel diseases should undergo clinical and genetic screening to protect them from SCD. The affected families should be investigated systematically so that appropriate diagnoses and treatments can be established.

Prevalence and associated factors of ECG abnormality patterns indicative of cardiac channelopathies among adult general population of Tehran, Iran: a report from the Tehran Cohort Study (TeCS)

BackgroundThe characteristics of electrocardiogram (ECG) abnormalities related to cardiac channelopathies potentially linked to sudden cardiac death (SCD) are not widely recognized in Iran. We examined the prevalence of such ECG patterns and their related factors among adult residents of Tehran, Iran.MethodsThe clinical characteristics and 12-lead ECGs of Tehran Cohort Study participants were examined. Long QT intervals, short QT intervals, Brugada syndrome (BrS) patterns, and early repolarization (ER) were evaluated using computer-based assessment software validated by cardiologists. Logistic regression models were employed to identify the factors associated with the prevalence of different ECG patterns.ResultsOut of 7678 available ECGs, 7350 were included in this analysis. Long QT interval, ER pattern, BrS patterns, and short QT interval were found in 3.08%, 1.43%, 0.31%, and 0.03% of participants, respectively. The prevalence of long QT interval increased with age, opium consumption, and presence of hypertension. Younger age, lower body mass index (BMI), alcohol use and male sex were independently linked to an elevated prevalence of ER pattern. Most individuals with BrS patterns were men (95%) and had lower BMI, high- and low-density lipoprotein, and total cholesterol compared to those without the BrS pattern. At a mean follow-up of 30.2 ± 5.5 months, all-cause mortality in the group exhibiting abnormal ECG patterns (6.3%) was approximately twice as high as that in the group without such patterns (2.96%).ConclusionAbnormal ECG patterns corresponding to channelopathies were relatively rare among adult residents of the Tehran population, and their prevalence was influenced by various factors.Clinical trial numberNot applicable.

Drug-induced increase in dispersion of ventricular repolarization in patients with heart failure with preserved ejection fraction

BackgroundHeart failure (HF) with preserved ejection fraction (HFpEF) is associated with enhanced response to drug-induced QT interval lengthening. We determined the influence of HFpEF on drug-induced lengthening of dispersion of repolarization, a measure of proarrhythmic risk. MethodsWe administered intravenous ibutilide 0.003 mg/kg to 10 patients with HFpEF and 10 age- and sex-matched controls without HF. Twelve‑lead electrocardiograms were obtained prior to ibutilide and serially for 8 h post-ibutilide. Tpeak-Tend, a measure of dispersion of ventricular repolarization, and heart rate-corrected J-Tpeak (J-Tpeakc), representing early repolarization, were measured by an investigator blinded to study groups. ResultsBaseline (pre-ibutilide) Tpeak-Tend and J-Tpeakc were not significantly different in the HFpEF and control groups. Maximum Tpeak-Tend was longer in the HFpEF group than in the control group (85 ± 10 vs 73 ± 8 ms, p = 0.01). Additionally, % change from baseline in Tpeak-Tend was greater in the HFpEF group [median (IQR) 17 (11) vs 8 (3)%, p = 0.003]. The area under the effect curve from 0 to 8 hours following ibutilide (including the 10-minute infusion) (AUEC0-8.17) for Tpeak-Tend was also larger in the HFpEF group (600 ± 42 vs. 543 ± 49 ms•hr, p = 0.03). Maximum J-Tpeakc, % change from baseline in J-Tpeakc and AUEC0-8.17 for J-Tpeakc in the two groups were not significantly different. ConclusionHFpEF is associated with enhanced response to drug-induced increases in dispersion of repolarization.

Electrocardiographic abnormalities are frequently detected in healthy adult Borzoi with a normal echocardiogram.

Borzoi reportedly experience sudden death. The objective of this study was to report ECG intervals, amplitudes, and frequency of ECG abnormalities in clinically healthy Borzoi. 98 clinically healthy Borzoi were prospectively recruited and underwent echocardiogram, ECG, and cardiac troponin I testing between October 2020 and December 2022. Standard ECG measurements were obtained. Early repolarization notches and slurs were recorded. Of 82 Borzoi with a structurally normal echocardiogram, ventricular arrhythmias were documented in 8 (10%) dogs, all of which had normal cardiac troponin I concentrations. Median P wave duration was 55 milliseconds (range, 45 to 70 milliseconds). Median PR interval was 125 milliseconds (range, 80 to 175 milliseconds). Thirty-one (38%) Borzoi had first-degree atrioventricular block (PR interval > 130 milliseconds). Median QRS duration was 65 milliseconds (range, 48 to 90 milliseconds). Median QT interval was 235 milliseconds (range, 185 to 275 milliseconds). Twenty-nine (35%) and 15 (18%) of 82 Borzoi had QT intervals > 240 or > 250 milliseconds, respectively. Sixty-seven of 82 (82%) Borzoi had early repolarization notches or slurs. Seventeen of 82 (21%) Borzoi had an abnormality of the ST segment, most commonly convexity/doming. Convexity of the ST segment was intermittent (n = 9) or persistent (4). Ventricular arrhythmias, early repolarization, prolonged QT intervals, and ST segment abnormalities are not infrequent in clinically healthy Borzoi. P, PR, and QRS durations are commonly prolonged compared to general canine reference intervals. Future study into heritable channelopathies in Borzoi is warranted given the frequency of ventricular arrhythmias, repolarization abnormalities, and sudden death in the breed. Breed-specific ECG reference intervals are needed.

Reaction of young physically active men with early repolarization phenomena on a cycle of inhalations of a hypoxic gas mixture

Aim: To examine a reaction of young physically active men with early repolarization phenomena (ERP) on an inhalation of a hypoxic gas mixture (IHGM).Material and Methods.17 men (6 with ERP & 11 without it) participated in our study. ECG, echocardiography, clinical blood test and erythropoietin blood test were carried out to every of them initially and on the 1-st and 10-th days after the IHGM.Results. It was found that end systolic volume was 13,8% more (р = 0,01) and ejection fraction was 8% less (р = 0,01) in ERP group than in non ERP group. These indicators were not change after IHGM. In ERP group on 1-st day after IHGM erythropoietin concentration was 79% more (р = 0,027) and on a 10-th day was 64% more (р = 0,003) than in non-ERP group. In ERP group high fluorescent reticulocyte count on a 1-st day after IHGM was 69% more (р = 0,03) and middle fluorescent reticulocyte count on a 10-th day after IHGM was 13% more (р = 0,04) than in non-ERP group. On a 10-th day after IHGM hematocrit and hemoglobin concentration were 5% (р = 0,01) and 12% (р = 0,01) less than in non ERP group.Conclusion. Thus, men with ERP have a pronounced reaction of the erythropoiesis system on normobaric hypoxia.

Investigation of Electrocardiographic Changes in Individuals with Three or More Cardiovascular Risk Factors on Santiago Island-The Cross-Sectional PrevCardio.CV Study.

Cerebrocardiovascular diseases represent one of the greatest public health concerns globally. In Cabo Verde, non-communicable diseases, such as cerebrocardiovascular diseases, have become leading causes of morbidity and mortality. This study aimed to correlate risk factors with cardiac electrical changes in adult individuals residing on Santiago Island-Cabo Verde. A cross-sectional population-based study using simple random sampling was conducted in 2021 with individuals aged 18 and over, of both sexes, having authorization 35/2021 from the Cabo Verde Ethics Commission. The sample size was calculated based on Santiago Island's projected population for 2021, considering an estimated prevalence of 50%, a 95% confidence interval, and a standard error of 4%, resulting in a sample of 599 individuals. The data were collected through a questionnaire on risk factors and cerebrocardiovascular diseases, blood pressure measurement, capillary blood glucose evaluation, and a 12-lead electrocardiogram. The study sample was predominantly female (54.8%), with the largest age group being 18-27 years (21%). Among the sample, 9.3% had no risk factors, 27.5% had one risk factor, 36.2% had two risk factors, and 26.9% had three or more risk factors. Of those who underwent electrocardiography, 60.24% showed electrocardiographic changes, with the most prevalent being ventricular repolarization changes, nonspecific repolarization changes, and early repolarization. A relationship was observed between cerebrocardiovascular disease risk factors and the electrocardiographic changes found in the study participants.

PITX2 deficiency leads to atrial mitochondrial dysfunction.

Reduced left atrial PITX2 is associated with atrial cardiomyopathy and atrial fibrillation. PITX2 is restricted to left atrial cardiomyocytes in the adult heart. The links between PITX2 deficiency, atrial cardiomyopathy and atrial fibrillation are not fully understood. To identify mechanisms linking PITX2 deficiency to atrial fibrillation, we generated and characterized PITX2-deficient human atrial cardiomyocytes derived from human induced pluripotent stem cells (hiPSC) and their controls. PITX2-deficient hiPSC-derived atrial cardiomyocytes showed shorter and disorganised sarcomeres and increased mononucleation. Electron microscopy found an increased number of smaller mitochondria compared to the control. Mitochondrial protein expression was altered in PITX2-deficient hiPSC-derived atrial cardiomyocytes. Single-nuclear RNA-sequencing found differences in cellular respiration pathways and differentially expressed mitochondrial and ion channel genes in PITX2-deficient hiPSC-derived atrial cardiomyocytes. PITX2 repression in hiPSC-derived atrial cardiomyocytes replicated dysregulation of cellular respiration. Mitochondrial respiration was shifted to increased glycolysis in PITX2-deficient hiPSC-derived atrial cardiomyocytes. PITX2-deficient human hiPSC-derived atrial cardiomyocytes showed higher spontaneous beating rates. Action potential duration was more variable with an overall prolongation of early repolarization, consistent with metabolic defects. Gene expression analyses confirmed changes in mitochondrial genes in left atria from 42 patients with atrial fibrillation compared to 43 patients in sinus rhythm. Dysregulation of left atrial mitochondrial (COX7C) and metabolic (FOXO1) genes was associated with PITX2 expression in human left atria. In summary, PITX2 deficiency causes mitochondrial dysfunction and a metabolic shift to glycolysis in human atrial cardiomyocytes. PITX2-dependent metabolic changes can contribute to the structural and functional defects found in PITX2-deficient atria.

Anxiety and depression in a patient with an implantable cardioverter defibrillator for early repolarization syndrome: A case report and clinical discussion

Early repolarization syndrome (ERS) was initially thought to be a good prognostic manifestation detectable by electrocardiogram. In recent years, with the gradual deepening of research and understanding, ERS is considered to possess malignant tendency and related to ventricular fibrillation (VF) and sudden cardiac death (SCD). Implantable cardioverter defibrillator (ICD) is currently the first choice of treatment used to reduce the risk of potentially life-threatening arrhythmias and SCD in patients at high risk for ERS. The stress of living with an implanted device and receiving ICD shock has been noted to exert a psychological toll on patients, especially those who have previously experienced VF and syncope. The current case report describes symptoms and signs of a patient with ERS, and discusses the changes of psychological condition after ICD implantation. Moreover, we explored a targeted treatment approach for anxiety and depression in an individual with an ICD for ERS, which combined medication, cognitive behavioral therapy, and physical exercise. We believe that the psychological experience of ICD recipients, which is a critical component in designing the biopsychosocial therapeutic approach for this growing patient population, is worthy of more attention.

Late gadolinium enhancement in early repolarization syndrome

BackgroundIn patients with Brugada syndrome, myocardial fibrosis can be identified through epicardial biopsy or cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE). However, the myocardial alterations in patients with early repolarization syndrome (ERS) remain poorly elucidated. ObjectiveThe objective of this study was to investigate the presence of myocardial fibrosis in patients with ERS by LGE in CMR. MethodsWe retrospectively evaluated 20 patients with ERS, all of whom exhibited J waves in the contiguous 2 leads. The location of J waves was classified as in the septum (V1-V2), anterior (V3-V4), lateral (I, aVL, V5-V6), inferior (II, III, aVF), or posterior (V7-V9) regions. To compare the distribution of LGE on CMR imaging with J waves, sections on short-axis view of the left ventricle (LV) were categorized as located in the septum, anterior, lateral, inferior, and posterior regions. ResultsOverall, 85% of ERS patients displayed LGE, which was more prevalent in the septum and posterior regions, followed by the inferior and lateral regions. The presence or absence of J waves and LGE coincided in 61% of LV areas, whereas discordance between the distributions of J waves and LGE was observed in 38%. LGE was most frequent in the septum (75%), where its reflection in J waves may be less robust. The appearance of LGE was not associated with symptoms, electrical storm, or ventricular fibrillation occurrence during follow-up. ConclusionLGE is common in patients with ERS, and the distribution of J waves and LGE coincides in approximately 60% of LV areas.

The Clinical Relevance of ECG Parameters in the Prediction of Cardiac Mortality: A Comprehensive Review

About half of all heart disease deaths are caused by cardiac arrest, making it one of the major causes of mortality in prosperous countries. When confronted with potentially fatal arrhythmias, implanted preventive cardioverter defibrillators significantly improve survival chances. However, this is only possible if high-risk patients who are prone to spontaneous cardiac arrest are identified beforehand. The current analysis examines the most recent findings regarding the use of surface electrocardiogram (ECG) data to predict sudden cardiac arrest. Here, we provide a comprehensive overview of the literature on non-invasive ECG techniques for predicting these kinds of cardiovascular crises. Several electrocardiographic risk stratification methods, including T-wave alternans, signal-averaged ECG, T-peak-to-end variation, early repolarization, an extension of the QT interval, QRS duration, QRS cluster patterns, and Holter monitoring, have been reviewed and analysed. These ECG results have shown to be useful as first screening instruments. Nonetheless, no single ECG measure has shown to be an effective technique for classifying individuals based on their risk of sudden cardiac arrest to date. Nevertheless, one or more of these prospective SEM metrics might potentially be important in intricate risk categorization schemes.

Optimized J to T peak and T peak to T end measurements in nonclinical species administered moxifloxacin and amiodarone

IntroductionCardiovascular safety and the risk of developing the potentially fatal ventricular tachyarrhythmia, Torsades de Pointes (TdP), have long been major concerns of drug development. TdP is associated with a delayed ventricular repolarization represented by QT interval prolongation in the electrocardiogram (ECG), typically due to block of the potassium channel encoded by the human ether-a-go-go related gene (hERG). Importantly however, not all drugs that prolong the QT interval are torsadagenic and not all hERG blockers prolong the QT interval. Recent clinical reports suggest that partitioning the QT interval into early (J to T peak; JTp) and late repolarization (T peak to T end; TpTe) components may be valuable for distinguishing low-risk mixed ion channel blockers (hERG plus calcium and/or late sodium currents) from high-risk pure hERG channel blockers. This strategy, if true for nonclinical animal models, could be used to de-risk QT prolonging compounds earlier in the drug development process. MethodsTo explore this, we investigated JTp and TpTe in ECG data collected from telemetered dogs and/or monkeys administered moxifloxacin or amiodarone at doses targeting relevant clinical exposures. An optimized placement of the Tpeak fiducial mark was utilized, and all intervals were corrected for heart rate (QTc, JTpc, TpTec). ResultsIncreases in QTc and JTpc intervals with administration of the pure hERG blocker moxifloxacin and an initial QTc and JTpc shortening followed by prolongation with the mixed ion channel blocker amiodarone were detected as expected, aligning with clinical data. However, anticipated increases in TpTec by both standard agents were not detected. DiscussionThe inability to detect changes in TpTec reduces the utility of these subintervals for prediction of arrhythmias using continuous single‑lead ECGs collected from freely moving dogs and monkeys.

Sex differences of 12 lead electrocardiographic findings of the rugby football league athlete

Cardiac electrical adaptations occur within athlete populations. Sex-related variations in the normal athlete electrocardiogram (ECG) have been observed, with males exhibiting increased QRS and PR intervals, while females have demonstrated increased QTc intervals in university-level athletes. Male athletes also maintain greater weekly training hours compared to female athletes, which is associated with increased ECG changes. The presence of these differences within Rugby Football League (RFL) athletes is unknown. This study aimed to investigate any sex-related variations in the 12-lead ECG in RFL athletes. Fifty nine RFL athletes (32 males [age = 25 ± 5 years] and 27 females [age = 24 ± 5 years]) were included in the study. One female was excluded with inferior T wave inversion and was referred for further investigation. The 12-lead ECG was collected as part of the athlete’s pre-season cardiac screening alongside completion of a health questionnaire, assessment of height and weight and brachial artery pressure. Continuous variables (i.e. heart rate, PR interval, QRS interval etc.), were analysed using an independent t-test or a Mann-Whitney U test as appropriate. For assessment of nominal data (i.e. incidence of early repolarisation and junctional rhythm etc.) a chi-squared test or Fishers exact test were used. A Spearman’s correlation coefficient was used to determine any association between training hours and ECG findings. Ethics approval was obtained from Liverpool John Moores University Ethics Committee. Height (183 ± 5 vs. 169 ± 5 cm, P <0.001), weight (95 ± 11 vs. 77 ± 11 kg, P <0.001) and weekly training hours (18 ± 5 vs. 12 ± 5 hrs, P = 0.001) were higher in male athletes. PR interval (156 ± 34 vs. 142 ± 19 ms, P = 0.002), QRS duration (98 ± 9 vs. 88 ± 7 ms, P <0.001) and incidence of early repolarisation (47% vs. 11%, P = 0.004) were greater in males. Heart rate (57 ± 9 vs. 63 ± 11 bpm P = 0.016) and QTc interval (391 ± 20 vs. 414 ± 17 ms, P <0.001) were greater in females. There was a significant negative correlation between weekly training hours and QTc interval (rs = −0.355, P = 0.009) only. In conclusion, there are significant sex-related ECG differences within RFL athletes that partially mirror previous research. These findings emphasise the importance of considering sex-related variations, during cardiac screening on RFL athletes and enhance our understanding of the normal RFL athlete ECG.

A case of early repolarization syndrome in which hyponatremia and coronary vasospasms induced ventricular fibrillation

A 60-year-old man was referred to our hospital presenting with unconsciousness due to severe hyponatremia. The twelve‑lead ECG on admission exhibited prominent J waves in the inferolateral leads. During the treatment for hyponatremia, ventricular fibrillation (VF) occurred and the electrogram (ECG) after the VF incident exhibited marked ST elevation in the inferolateral leads. An Ach provocation test induced vasospasms in the right and left coronary arteries and J wave augmentation, suggesting a high risk for vasospastic angina. Finally, a subcutaneous implantable cardioverter defibrillator was implanted in the patient. We hereby discuss the possible contribution of hyponatremia to VF episodes in early repolarization syndrome based on the present case.

Electrocardiographic characteristics and catheter ablation of premature ventricular complex- mediated ventricular fibrillation

Abstract Background Premature ventricular contractions (PVCs) can trigger ventricular fibrillation (VF) in patients with/or without structural heart disease. There are limited data on coexisting electrocardiographic (ECG) features and catheter ablation outcomes in these patients which could suggest the concomitant presence of an abnormal electrical and structural substrate. Purpose We investigated ECG and electroanatomic characteristics and clinical outcomes in patents who underwent catheter ablation of PVCs triggering VF. Methods We analyzed data from a consecutive series of patients who underwent catheter ablation between 08/2019 and 04/2023 for PVCs triggering VF. On the 12-lead ECG, we assessed the following abnormalities: (a) Early repolarization (ER) pattern in either inferior or lateral leads (Figure 1), or (b) QRS Notching of either the native sinus beat or PVC (Figure 2). Post-ablation follow up outcomes were collected using a combination of ICD interrogation, remote transmission and clinical follow up. Results The cohort included 15 patients: age 52.1±16.8 years, 46.7% females, and 26.7% presenting with VF storm. On average, there were 3.8 HV shocks/per patient from an ICD prior to the index ablation procedure (range: 0-19 shocks). On the 12-lead ECG, the mean coupling interval of the PVC leading to VF was 204±82 ms, and an overall narrow PVC morphology with a mean QRS duration of 107±17 ms. We observed early repolarization (ER) in 6 (40%) of the cohort. In most patients (n=11; 73.3%), at least one of the 2 ECG abnormalities were present. An endocardial-only approach was adequate in all patients, and during catheter ablation, Purkinje potentials were targeted in 10 (66%) of the patients. Based on activation and pace-mapping, the PVCs were localized to the following sites: (a) left ventricular (LV) septum in 11 (73.3%), (b) papillary muscles in 2 (13.3%), and (c) other sites such as the Moderator band and right ventricular outflow tract in the remaining 2 (13.3%) patients. The ablation locations on the LV septum extended from basal to mid-septum. After an average of 1.7 ablation procedures targeting PVC-triggering VF, 12 (80%) patients remained free of sustained ventricular arrhythmias and ICD shocks, over a mean follow up of 479±395 days. Conclusion In most patients with PVCs-triggering VF, there was an evidence of an ECG abnormality either in the form of an ER pattern or notching of either the Sinus QRS or the PVC complex on pre-ablation ECG. During ablation, Purkinje potentials and PVCs were mapped to and ablated in the region of the LV interventricular septum and papillary muscles. Over long-term follow up, catheter ablation seemed durable and effective in reducing VF episodes and ICD shocks.Presence of Early Repolarization patternPresence of a notching pattern in the Si

High-resolution repolarization changes preceding short-coupled ectopy in idiopathic ventricular fibrillation, and effects of quinidine

Abstract Background Idiopathic ventricular fibrillation (VF) is linked to early repolarization, increased repolarization heterogeneity, and (short-coupled) premature ventricular complexes (PVCs). Quinidine, an antiarrhythmic drug with class-IA and -III effects, reduces the occurrence of PVCs and VF, but its effects on repolarization have not yet been studied at the whole-heart level in idiopathic-VF patients. Purpose To study dynamic changes in repolarization preceding short-coupled PVCs using noninvasive electrocardiographic imaging (ECGI) in a patient with idiopathic VF, and the antiarrhythmic effects of quinidine. Methods ECGI was performed during sinus rhythm in a 61-year-old male with an ICD (secondary prevention; 2.5 mg nebivolol daily) two days after recurrent idiopathic VF (Fig. A). This was done 1) at baseline, 2 minutes before short-coupled ectopy ("baseline"); 2) at baseline, 10 seconds before the short-coupled PVC ("pre PVC"); and 3) at 2 hours after start of quinidine 200 mg ("on-quinidine"). The ECGI procedure consisted of a 224-electrode body surface potential map and a contrast-enhanced CT scan to obtain torso and heart geometries. After reconstruction of epicardial unipolar electrograms (UEGs), local activation and repolarization times (ATs and RTs) were derived from UEGs by assessing the steepest downslope of the QRS complex and steepest upslope of the T waves, respectively, of 10-second signal-averaged beats. AT and RT duration (first to last AT or RT) were assessed. Results At baseline, QRS duration and QT interval measured 107 ms and 343 ms, respectively, on the standard 12-lead ECG. ECGI-derived epicardial AT duration was 72 ms, and RT histogram span 92 ms. The coupling interval of the PVC that triggered VF in the ICD readout was 340 ms (Fig. A). During 44 minutes of ECGI, 157 short-coupled PVCs from the moderator-band region were recorded (Fig. B; no tachycardia or VF). Just prior to a PVC, epicardial early repolarization at the PVC origin decreased by 26 ms (star in Figs. C-E), and the RT histogram broadened to 109 ms (Fig. E). While on-quinidine, (25 minutes; QRS duration 107 ms, QT interval 419 ms), epicardial repolarization was prolonged (Fig. C/D), also at the site of abnormal impulse formation. Quinidine had increased the epicardial AT duration to 79 ms, and RT histogram span to 133 ms. PVCs were completely suppressed. The patient remained free of sustained arrhythmias while on-quinidine. Conclusion(s) In this case of short-coupled idiopathic VF, epicardial early repolarization shortened momentarily prior to abnormal impulse formation. We found dynamic substrate-trigger characteristics that likely facilitate reentrant excitation. Quinidine prolonged the duration of epicardial activation and repolarization, suppressing the ectopy and VF recurrence.

Evolution of the ECG in idiopathic ventricular fibrillation survivors: results from a single-centre UK registry

Abstract Background Idiopathic ventricular fibrillation (VF) is a diagnosis of exclusion in subjects with an unexplained cardiac arrest and no evidence of overt structural or electrical cardiac abnormalities (1). It can be associated with an early repolarisation pattern (ERP)(2). Data on the evolution of the ECG in this population are lacking. Purpose To compare the baseline ECG characteristic of idiopathic VF survivors and age and gender matched controls, and investigate if the presence of an ERP at ECG is a predictor of risk. Methods Forty-nine subjects with idiopathic VF evaluated in our tertiary centre from 1997 to 2022, and followed-up for at least 3 months were included in this study. The first representative ECG available after cardiac arrest was evaluated and compared with that of an age and gender matched control with no symptoms, family history of sudden cardiac death and normal cardiac tests; moreover, comparison was made with a follow-up ECG off antiarrhythmic medications (quinidine, amiodarone and verapamil). Medical notes were reviewed to investigate the presence of events at f-up (SCD/appropriate ICD shock). Results The mean age at presentation was 33±7 years; 63% of patients were males, and 16% had previous syncope. Twelve cases (24%) and 6 controls (12%) showed ERP on the resting ECG (P=NS). Only resting heart rate (HR) and QRS duration differed between the two groups (Table 1). Follow-up ECGs in 46 idiopathic VF survivors indicated that resting HR, QRS axis and QTc values were significantly different compared to the baseline ECG. In addition, 4 subjects with ERP at baseline did not exhibit it on the most recent ECG, and 6 subjects without ERP at baseline showed it on the most recent ECG. Over a median follow-up of 3.3 years (IQR 6), 13 subjects experienced appropriate ICD shocks. Kaplan-Meyer survival estimates showed no differences in events between subjects showing ERP or not (log rank p=0.092). Conclusions Subjects with idiopathic VF show baseline ECGs similar to those of age and gender matched healthy controls from the general population. ECG parameters tend to change only slightly over long-term follow up. The ERP in idiopathic VF survivors is dynamic and thus its relationship with events may be underestimated.Table 1 Table 2

Association between early repolarization and vagally mediated atrial fibrillation

Association between early repolarization and vagally mediated atrial fibrillation

MYOCARDIAL INFARCTION DUE TO LEFT CIRCUMFLEX ARTERY OCCLUSION: A SUBTLE TROJAN HORSE

Abstract A 47–year–old man presented to the emergency department complaining of recurrent chest pain (CP) since the previous day. His medical history included active smoking and dyslipidemia. The ECG revealed sinus bradycardia (56 bpm) with widespread ST elevation, consistent with benign early repolarization, and hyperacute and broad–based T waves in V2–V3 (Fig. A). The echocardiography showed normal left and right ventricular systolic function and no valvular abnormalities. A low but abnormal initial high–sensitivity cardiac troponin I value (40 pg/mL, normal range: 1.7– 34,2 pg/mL) and a slightly and early increase after two hours (52 pg/ml) were seen. Therefore, the patient was admitted to our intensive cardiac care unit (ICCU) with a working diagnosis of non–ST–segment elevation myocardial infarction (NSTEMI). No sign or symptoms of heart failure on physical examination were recorded. GraceScore 2.0 was calculated as 68 points and coronary angiography was organized within 24h. Two hours after admission to the ICCU, the patient experienced a new episode of CP. Consequently, ECG and echo were repeated. Compared to the previous results, ECG showed dynamic changes in V2–V3, with the resolution of hyperacute T waves (Fig B); bedside echo remained unchanged. Considering the unresponsiveness to nitrate therapy, the cath lab was activated for a time–dependent coronary angiography. The exam showed an acute total thrombotic occlusion of the mid–segment of the circumflex branch (LCx) in the setting left–sided dominant circulation. A drug eluting stent was deployed into the culprit lesion (Fig. C), and the coronary flow was restored completely (TIMI Flow 3). The subsequent hospital stay proceeded without complications. The peak troponin level was 60’000 pg/ml. The patient was discharged on the fifth day, asymptomatic and hemodynamically stable, with instructions to continue dual antiplatelet therapy. The case report focuses on the electrocardiographic and angiographic expression of LCx total occlusion. Despite acute myocardial infarction (AMI) size was large, as confirmed by the abnormal troponin I values and the angiographic total occlusion, the first and the repeated ECGs showed only vague repolarization changes without clear ST–segment modifications. LCx occlusion is often characterized by the absence of significant ST–elevation, therefore categorized as NSTEMI. Greater awareness of the presentation of LCx–related AMI can be crucial to avoid delays in reperfusion.