Surface ECG Research Articles

Evaluation of the Correlation Between Electrocardiographic Abnormalities, Cardiac Iron Overload, and Magnetic Resonance T2* Values in Patients with Beta Thalassemia Major

Background: Beta thalassemia major (β-TM) is an inherited blood disorder. Affected patients require frequent blood transfusions, leading to iron deposition and end organ damage, particularly myocardial dysfunction. A 12-lead ECG is a readily available tool that could be used to screen for conduction abnormalities and arrhythmias as a marker of worsening myocardial function. Methods: A total of 108 β-TM patients were evaluated for correlation between abnormal findings on the surface ECG and severity of myocardial iron deposition in magnetic resonance imaging as measured by T2* levels. Results: Patients with T2* below 20 msec had significantly longer PR intervals, P wave durations, and QTc intervals. Patients with T2* below 10 msec had the longest QRS duration and QRS activation times. Atrial fibrillation was more prevalent in patients with lower T2* levels. With a decrease in T2*, the probability of notching of QRS in the limb and precordial leads increased. Conclusion: Abnormal ECG is prevalent in β-TM patients, and the frequency of changes increases with the severity of iron overload. A 12-lead ECG is a valuable and readily available tool for the early assessment of myocardial damage and the implementation of a timely and appropriate management strategy.

Clinical, electrical, and functional changes following CRT-P implantation: short-term results in patients with non-ischaemic cardiomyopathy

Aim. Assessment of the correlation between cardiac remodeling, functional status and electrical remodeling after cardiac resynchronisation therapy (CRT) in patients with non-ischaemic cardiomyopathy.Material and methods. A single center, prospective, observational study included 50 patients with non-ischaemic cardiomyopathy who were candidate for CRT implantation. All patients prior to CRT and then 3 months after implantation had standard 12-lead surface ECGs to assess QRSd for assessment electrical response, for assessment of left ventricular ejection fraction (LVEF) and volumes (left ventricular end diastolic and systolic volume, LVEDV and LVESV), mitral regurgitation (degree of mitral regurgitation), pulmonary artery systolic pressure (for diagnosis of pulmonary hypertension), NYHA class and 6 minute walk test (6MWT) to assess patient’s functional capacity.Results. 50 patients with CRT were included (35 males and 15 females, mean age 54.88±7.48 years). All patients were in sinus rhythm with QRS duration (QRSd) ≥120 ms, EF<35% and left bundle branch block. After 3 months; there was significant improvement in QRSd in 82% of the cases (145.3±16.3 ms vs 133.3±17.2 ms, p<0.001). NYHA class improved at least one class in 78% and 6 min walk test improved in 80% (168.5 [131.0; 181.0] m vs 280.0 [237.0; 297.0] m, p<0.001). LVEF increased significantly in 74% of study cases (28.6±2.7 vs 34.5±3.1, p value 0.001) also there were statistically significant improvement in LVEDV (267.0±45.7 to 221.8±41.9 ml, p=0.002) and LVESV (137.43±47.19 to 105.03±42.7 ml, p=0.003). There was statistically significant correlation between QRSd and NYHA class (r=0.392, p=0.005), QRSd and 6MWT (r=0.323, p=0.022) and QRSd with LVEF (r=0.672 with p<0.001). Only seven patients showed improvement in the 3 parameters: LVESV, QRS duration and 6 min walk test.Conclusion. The CRT-pacemaker implantation was associated with significant improvement in QRSd, NYHA class, 6MWT and LV volumes in the short-term period. QRSd improvement was significantly correlated with functional status and LV EF.

Risk of atrial fibrillation development in adolescent patients with inflammatory bowel disease.

There is increasing evidence linking chronic inflammation to the initiation and continuation of atrial fibrillation (AF). Inflammatory bowel diseases (IBD), namely (Crohn's disease (CD) and ulcerative colitis (UC), are chronic systemic inflammatory disorders with both intestinal and extra-intestinal manifestations. Atrial electromechanical delay (EMD) has been known as an early marker of AF. The objective of this study was to evaluate the atrial electromechanical properties in children and adolescents with IBD during remission. One hundred IBD patients aged 12-17 years (50 with CD and 50 with UC) in remission state and 100 healthy controls were recruited for the study. Atrial electromechanical properties were measured using transthoracic echocardiography, tissue Doppler imaging, and simultaneous surface ECG recording. Interatrial EMD, left intra-atrial, and right intra-atrial EMD were calculated. IBD patients in remission state have significantly prolonged left and right intra-atrial EMD and interatrial EMD compared to healthy controls (P = 0.03, P = 0.02, and P = 0.01 respectively). No statistical difference was observed between CD and UC in terms of inter- and intra-atrial EMDs. Conclusion:Atrial EMD is increased in pediatric patients with IBD indicating the increased risk of AF development. Measurement of atrial EMD parameters might be used to predict the risk of the development of AF in pediatric patients with IBD. What is Known: • There is increasing evidence linking chronic inflammation to the initiation and continuation of atrial fibrillation (AF). • Inflammatory bowel diseases are chronic systemic inflammatory disorders with both intestinal and extra-intestinal manifestations. • Atrial electromechanical delay (EMD) has been reported as an early marker of AF. What is New: • Atrial EMD is increased in pediatric patients with IBD indicating the increased risk of AF development. • Measurement of atrial EMD parameters might be used to predict the risk of the development of AF in pediatric patients with IBD.

Robust Artificial Intelligence Tool for Atrial Fibrillation Diagnosis: Novel Development Approach Incorporating Both Atrial Electrograms and Surface ECG and Evaluation by Head-to-Head Comparison With Hospital-Based Physician ECG Readers.

Atrial fibrillation (AF) increases risk of embolic stroke, and in postoperative patients, increases cost of care. Consequently, ECG screening for AF in high-risk patients is important but labor-intensive. Artificial intelligence (AI) may reduce AF detection workload, but AI development presents challenges. We used a novel approach to AI development for AF detection using both surface ECG recordings and atrial epicardial electrograms obtained in postoperative cardiac patients. Atrial electrograms were used only to facilitate establishing true AF for AI development; this permitted the establishment of an AI-based tool for subsequent AF detection using ECG records alone. A total of 5 million 30-second epochs from 329 patients were annotated as AF or non-AF by expert ECG readers for AI training and validation, while 5 million 30-second epochs from 330 different patients were used for AI testing. AI performance was assessed at the epoch level as well as AF burden at the patient level. AI achieved an area under the receiver operating characteristic curve of 0.932 on validation and 0.953 on testing. At the epoch level, testing results showed means of AF detection sensitivity, specificity, negative predictive value, positive predictive value, and F1 (harmonic mean of positive predictive value and sensitivity) as 0.970, 0.814, 0.976, 0.776, and 0.862, respectively, while the intraclass correlation coefficient for AF burden detection was 0.952. At the patient level, AF burden sensitivity and positive predictivity were 96.2% and 94.5%, respectively. Use of both atrial electrograms and surface ECG permitted development of a robust AI-based approach to postoperative AF recognition and AF burden assessment. This novel tool may enhance detection and management of AF, particularly in patients following operative cardiac surgery.

Case report: Para Hisian Atrial Tachycardia

Case report: Para Hisian Atrial Tachycardia

Intracardiac electrophysiology to characterize susceptibility to ventricular arrhythmias in murine models.

Introduction: Sudden cardiac death (SCD) and ventricular fibrillation are rare but severe complications of many cardiovascular diseases and represent a major health issue worldwide. Although the primary causes are often acute or chronic coronary diseases, genetic conditions, such as inherited channelopathies or non-ischemic cardiomyopathies are leading causes of SCD among the young. However, relevant experimental models to study the underlying mechanisms of arrhythmias and develop new therapies are still needed. The number of genetically engineered mouse models with cardiac phenotype is growing, making electrophysiological studies in mice essential tools to study arrhythmogenicity and arrhythmia mechanisms and to test novel treatments. Recently, intracardiac catheterization via the jugular vein was described to induce and record ventricular arrhythmias in living anesthetized mice. Several strategies have been reported, developed in healthy wild-type animals and based on aggressive right ventricular stimulation. Methods: Here, we report a protocol based on programmed electrical stimulation (PES) performed in clinical practice in patients with cardiac rhythm disorders, adapted to two transgenic mice models of arrhythmia - Brugada syndrome and cardiolaminopathy. Results: We show that this progressive protocol, based on a limited number of right ventricular extrastimuli, enables to reveal different rhythmic phenotypes between control and diseased mice. In this study, we provide detailed information on PES in mice, including catheter positioning, stimulation protocols, intracardiac and surface ECG interpretation and we reveal a higher susceptibility of two mouse lines to experience triggered ventricular arrhythmias, when compared to control mice. Discussion: Overall, this technique allows to characterize arrhythmias and provides results in phenotyping 2 arrhythmogenic-disease murine models.

A machine learning approach to differentiate wide QRS tachycardia: distinguishing ventricular tachycardia from supraventricular tachycardia.

Differential diagnosis of wide QRS tachycardia (WQCT) has been a challenging issue. Published algorithms to distinguish ventricular tachycardia (VT) and supraventricular tachycardia (SVT) have limited diagnostic capabilities. A total of 278 patients with WQCT from January 2010 to March 2022 were enrolled. The electrophysiological study confirmed SVT in 154 patients and VT in 65 ones. Two hundred nineteen WQCT 12-lead ECGs were randomly divided into development cohort (n = 165) and testing cohort (n = 54) data sets. The development cohort was split into a training group (n = 115) and an internal validation group (n = 50). Forty ECG features extracted from the 219 WQCT ECGs are fed into 9 iteratively trained ML algorithms. This novel ML algorithm was also compared with four published algorithms. In the development cohort, the Gradient Boosting Machine (GBM) model displayed the maximum area under curve (AUC) (0.91, 95% confidence interval (CI) 0.81-1.00). In the testing cohort, the GBM model had a higher AUC of 0.97 compared to 4 validated ECG algorithms, namely, Brugada (0.68), avR (0.62), RWPTII (0.72), and LLA algorithms (0.70). Accuracy, sensitivity, specificity, negative predictive value, and positive predictive value of the GBM model were 0.94, 0.97, 0.90, 0.94, and 0.95, respectively. A GBM ML model contributes to distinguishing SVT from VT based on surface ECG features. In addition, we were able to identify important indicators for distinguishing WQCT.

Acute alcohol exposure and electrocardiographic changes: Finding from the HOLIDAY trial

BackgroundAlcohol consumption is associated with a higher increased risk of atrial fibrillation (AF), but the acute effects on cardiac electrophysiology in humans remain poorly understood. The HOw ALcohol InDuces Atrial TachYarrhythmias (HOLIDAY) Trial revealed that alcohol shortened pulmonary vein atrial effective refractory periods, but more global electrophysiologic changes gleaned from the surface ECG have not yet been reported. MethodsThis was a secondary analysis of the HOLIDAY Trial. During AF ablation procedures, 100 adults were randomized to intravenous alcohol titrated to 0.08% blood alcohol concentration versus a volume and osmolarity-matched, masked, placebo. Intervals measured from 12‑lead ECGs were compared between pre infusion and at infusion steady state (20 min). ResultsThe average age was 60 years and 11% were female. No significant differences in the P-wave duration, PR, QRS or QT intervals, were present between alcohol and placebo arms. However, infusion of alcohol was associated with a statistically significant relative shortening of the JT interval (r: −14.73, p = 0.048) after multivariable adjustment. ConclusionAcute exposure to alcohol was associated with a relative reduction in the JT interval, reflecting shortening of ventricular repolarization. These acute changes may reflect a more global shortening of refractoriness, suggesting immediate proarrhythmic effects pertinent to the atria and ventricles.

Impact of Vernix Caseosa Distribution on Non-Invasive Fetal ECG Morphology: A Computational Study.

Accurate monitoring of fetal cardiac activity is paramount for the early detection of fetal pathologies during pregnancy. Non-invasive fetal ECG has shown promise, offering advantages over traditional fetal monitoring techniques such as cardiotocography. However, extracting fetal signals from maternal abdominal recordings poses challenges, particularly due to the presence of the vernix caseosa, a fatty layer surrounding the fetus. This study aims to investigate how vernix caseosa distribution influences ECG morphology in a novel computational framework. A multi-compartment volume conductor, integrating fetal and maternal hearts, fetal body, amniotic fluid, and vernix caseosa embedded in a maternal torso, is constructed. Vernix caseosa distribution is varied homogeneously and heterogeneously on the fetal body. Fetal cardiac activity is simulated using a pseudo-bidomain formulation. Resulting body surface potential and ECG is analysed in terms of RDM, lnMAG, QRS complex and T-wave morphology at six abdominal sensor placements. Results indicate vernix caseosa conductive properties and presence on the fetal head do not notably interfere with ECG readings, except in rare instances where the signal strength is extremely low. Signal strength is reduced more when covering back compared to front of the fetus. Nonetheless, both scenarios have a notable impact on ECG signal and T/QRS ratio, aligning with earlier findings suggesting caution in interpreting T/QRS ratio when vernix caseosa is present. The presence of vernix caseosa warrants careful consideration regarding ECG and especially T/QRS ratio interpretation. The study contributes to advancing the understanding of non-invasive fetal ECG.

Solving the Inverse Problem of Electrocardiography for Cardiac Digital Twins: A Survey.

Cardiac digital twins (CDTs) are personalized virtual representations used to understand complex cardiac mechanisms. A critical component of CDT development is solving the ECG inverse problem, which enables the reconstruction of cardiac sources and the estimation of patient-specific electrophysiology (EP) parameters from surface ECG data. Despite challenges from complex cardiac anatomy, noisy ECG data, and the ill-posed nature of the inverse problem, recent advances in computational methods have greatly improved the accuracy and efficiency of ECG inverse inference, strengthening the fidelity of CDTs. This paper aims to provide a comprehensive review of the methods of solving ECG inverse problem, the validation strategies, the clinical applications, and future perspectives. For the methodologies, we broadly classify state-of-the-art approaches into two categories: deterministic and probabilistic methods, including both conventional and deep learning-based techniques. Integrating physics laws with deep learning models holds promise, but challenges such as capturing dynamic electrophysiology accurately, accessing accurate domain knowledge, and quantifying prediction uncertainty persist. Integrating models into clinical workflows while ensuring interpretability and usability for healthcare professionals is essential. Overcoming these challenges will drive further research in CDTs.

Optimization of the system for predicting the severity of the course of COVID-19 in hospitalizedpatients based on cardiovascular history, initial clinical status and surface ECG indicators

The aim – to optimize the system of early assessment of the tendency to a more severe subsequent course of COVID-19, based on initial clinical, anamnestic and electrocardiographic markers.Materials and methods. Data from primary medical documentation on 104 patients with moderate severity of COVID-19 (50 men and 54 women, aged 24 to 84 years) who were treated (at least 16 days) in clinics of Ukraine during 2020–2021 were analyzed on the study of the effectiveness of the treatment of COVID-19. Risk factors (advanced age, inflammatory diseases, cardiovascular pathology: the presence of hypertension, obesity, diabetes, coronary artery disease, heart failure (HF), persistent or permanent atrial fibrillation (AF)), dynamics of the clinical state (HR, to body, blood pressure, SpO2, respiratory rate (HR), clinical symptoms and signs from all body systems), as well as surface ECG data in 12 leads were studied. Based on the dynamics of the clinical condition (according to a specially developed scale), all patients were divided into group A (66 pts, a more severe hospital course of COVID-19) and group B (38 pts, a milder variant of the course of COVID-19).Results and discussion. Among the electrocardiographic risk factors (RF) of a more severe hospital course of moderate-severe COVID-19, the following were more informative than others: a decrease in the amplitude of the Q wave in lead V5 (HR = 1.96 (95 % CI 1.29–2.96)) and an increase in the amplitude of the S wave in lead V4 (HR = 1.57 (95 % CI 1.18–2.08)), an increase in the duration of the QR interval in lead V1 (HR = 1.49 (95 % CI 1.11–2.0)) and its decrease – in leads V5–V6 (HR = 1.64 (95 % CI 1.3–2.1)), ST segment elevation in lead V4 (HR = 1.69 (95 % CI 1.43–2.00)), a low-amplitude T wave in lead I (HR = 1.60 (95 % CI 1.15–2.23)) and the appearance of abnormal TU complexes in leads V2–V6 (HR = 1.37 (95 % CI 1.04–1.80)), as well as a model built taking into account 8 ECG criteria (duration of the QR interval in lead V1 > 20 ms and in lead V5 < 24 ms, SI wave amplitude ratio to QII wave amplitude ratio > 4, R wave amplitude ratio in avL to QV5 wave amplitude ratio > 16, QR interval duration ratio in V1 to QR interval duration in V5 > 1, the ratio of ST elevation in V4 to the amplitude of the TI wave > 1), evaluated according to their significance (area under the ROC curve (ROC) 0.88, for values > 35 points HR = 2.43 (1.73–3.39)). When the 8-component ECG scale was combined with the components of the previously created clinical and anamnestic scales, the ROC increased to 0.93, the value > 48 points on the first day of COVID-19 with a sensitivity of 86 % and a specificity of 87 % (HR = 4.29 (2,4–7,69)) predicted a more severe variant of the hospital course of COVID-19 of moderate severity.Conclusions. The developed and optimized risk assessment system, based on clinical, anamnestic and electrocardiographic data, allows to accurately predict the subsequent more severe course of the disease on the first day of treatment for COVID-19. These results are promising from a practical point of view and require further study in a prospective study.

Increased circulating progranulin is not sufficient to induce cardiac dysfunction or supraventricular arrhythmia

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, and the incidence of new-onset AF has been increasing over the past two decades. Several factors contribute to the risk of developing AF including age, preexisting cardiovascular disease, chronic kidney disease, and obesity. Concurrent with the rise in AF, obesity has followed the same two-decade trend. The contribution of circulating proteins to obesity-related AF is of particular interest in the field. In this study, we investigated the effects of increased circulating levels of the glycoprotein progranulin on the development of supraventricular arrhythmias and changes to cardiac function. AAV8-mediated overexpression of full-length mouse progranulin was used to increase plasma protein levels and determine susceptibility to supraventricular arrhythmias and changes in cardiac structure and function. C57Bl/6N mice were subjected to increased circulating levels of progranulin for 20 weeks. Cardiac conduction was evaluated by surface ECG with and without isoproterenol challenge, and cardiac structure and function were measured by echocardiography after 20 weeks of circulating progranulin overexpression. Increased circulating levels of progranulin were maintained throughout the 20-week study. The cardiac structure and function remained unchanged in mice with increased circulating progranulin. ECG indices (P wave duration, P amplitude, QRS interval) were unaffected by increased progranulin levels and no arrhythmogenic events were observed following the isoproterenol challenge. In our model, increased levels of circulating progranulin were not sufficient to induce changes in cardiac structure and function or elicit ECG abnormalities suggestive of susceptibility to supraventricular arrhythmias.

Atrial fibrillation organisation correlates with ventricular response regularity in patients with persistent atrial fibrillation

Abstract Background Atrial fibrillation (AF) is characterised by an irregularly irregular ventricular rhythm. However, the mechanisms by which the regularity of ventricular response is influenced by AF dynamics is yet to be understood. In AF, there is a spectrum of organisation of atrial electrical activity; from organised AF sustained by focal drivers through to disorganised AF sustained by multiple wavelet re-entry. We aimed to investigate whether the ventricular response in AF was associated with the organisation of atrial electrical activity, with the hypothesis that AF organisation correlates with ventricular response regularity. Methods We retrospectively reviewed data from 239 patients with persistent AF undergoing pulmonary vein isolation (PVI). In each patient both before and after ablation, AF organisation and measures of ventricular variability and irregularity were evaluated in 50s segments. Shannon entropy (ShEn) and Sample entropy (SampEn) derived from coronary sinus (CS) atrial electrograms were used to assess AF organisation. RR interval (RRI) metrics derived from the surface ECG were used to determine ventricular variability and irregularity. RRI variability was evaluated using the time-domain measures: normalised mean RRI difference, standard deviation of RRIs (SD RRI), normalised SD RRI, root mean square of successive RRI differences (rMSSD) and percentage of successive RR intervals that differ from each other by more than 50ms (pNN50). RRI irregularity was measured using SampEn and normalised SampEn. Results A significant decrease in atrial ShEn and SampEn was observed following PVI across all CS channels (e.g. SampEn CS 3-4: pre-ablation=0.907±0.512 vs post-ablation=0.790±0.447, p<0.0001). Both ShEn and SampEn from CS atrial electrograms were significantly correlated with the RRI variability and irregularity measures from surface ECG (pNN50, normalised mean RRI difference, normalised SD RRI and normalised SampEn) both pre- and post-ablation (pNN50: r=0.0771, p=0.00838, Figure 1; normalised mean RRI difference: r=0.144, p<0.0001; normalised SD RRI: r=0.175, p<0.0001; normalised SampEn: r=0.168, p<0.0001; correlations with SampEn CS 3-4 pre-ablation shown). Conclusion The reduction in atrial ShEn and SampEn following PVI suggests that an increase in AF organisation occurs with PVI. The significant correlations between atrial entropy and measures of RRI variability and irregularity suggest that AF organisation impacts ventricular response regularity. Therefore, interpretation of the RRI variability and irregularity from the surface ECG may give some insight, non-invasively, into the level of AF organisation.Figure 1

Intracoronary ECG ST-segment shift remission time during reactive coronary hyperemia (tau-icECG): a new approach to assess hemodynamic coronary stenosis severity

Abstract Background Coronary pressure-derived fractional flow reserve (FFR) measurements are recommended for hemodynamic coronary stenosis assessment. Given temporary paralysis of the coronary microcirculation during hyperemia, pressure is, in theory, directly related to coronary flow. Pressure drop during hyperemia across a coronary stenosis, thus, provides an estimate of its restrictive effect on flow. FFR during reactive hyperemia induced by a proximal, 1-minute coronary artery balloon occlusion has been shown non-inferior to FFR as obtained by adenosine-induced hyperemia. Intracoronary ECG (icECG) is more sensitive in detecting myocardial ischemia than the surface ECG, and can be easily obtained. Purpose The present study evaluated a novel diagnostic approach based on icECG ST-segment shift remission time for hemodynamic stenosis severity assessment. Methods This was a retrospective observational trial in patients with chronic coronary syndrome, who underwent hemodynamic measurements during a brief coronary occlusion with simultaneous icECG recording during coronary angiography. The icECG recording was used for a beat-to-beat analysis of the ST-segment elevation performed by a previously developed fully autonomous algorithm. The time after release of the 1-minute ostial coronary balloon occlusion when the ST elevation reached 50% of the pre-occlusion (baseline) isoelectric line, i.e., icECG remission half time (τ-icECG; τ=tau), was obtained by the algorithm (Figure1). τ-icECG was evaluated using the simultaneously obtained FFR at a threshold of 0.80 as reference parameter. Results 139 icECGs from 119 patients were analysed, 23 had to be excluded in advance, due to incomplete icECG recording or algorithm failure. A ROC-analysis of τ at a threshold of >8s found it significantly accurate for detecting a hemodynamically relevant coronary stenosis at FFR≤0.80 (area under the ROC-curve 0.618, 95% CI 0.507-0.735, sensitivity 60%, specificity 67%, p=0.037) (Figure2). Conclusion Τ-icECG, a measure of icECG ST-elevation remission time to isoelectricity as obtained during reactive hyperemia FFR accurately detects hemodynamically relevant coronary artery stenoses at a threshold of ≥ 8 seconds.

High frame rate speckle tracking echocardiography to visualize the mechanical activation sequence of the left ventricle

Abstract Background Cardiac arrhythmias are a known cause of morbidity and mortality, with catheter ablation being an effective treatment. In order to detect the focal source or the re-entrant circuit of the arrhythmia, i.e. the ablation target, current practice includes performing an electrophysiological study. This technique is invasive, with increased patient related risk and variable success rate. Conversely, echocardiography could be used to determine the correct ablation target. High frame rate (HFR) ultrasound has a temporal resolution adequately high to detect the onset of myocardial deformation and could assist the accurate localisation of the arrhythmia source. Purpose To test whether HFR speckle tracking echocardiography (STE) can be used to create cardiac mechanical activation maps. Methods 18 healthy volunteers (HV) (age 30±6y; 69 %males) and 12 heart failure patients treated with cardiac resynchronisation therapy (CRT) (age 69±10y; 75 %males) were included. All participants were scanned with a research HFR ultrasound scanner (∼849fps) and the 3 standard apical views were acquired. Patients were scanned with CRT on and after turning CRT off, in order to allow intrinsic ventricular conduction. Data from one CRT patient were acquired by temporarily altering the pacing pole of the CRT LV lead. All patients had a left bundle branch block (LBBB) pattern of native activation on the surface ECG. For each view, a manually placed contour was tracked during the cardiac cycle by a custom-made 2D HFR STE algorithm; the contours were divided in a standard 16 segment model and segmental strain rate (SR) curves were computed and used to measure the temporal distance between electrical and mechanical activation (i.e. distance between the beginning of QRS and the first positive to negative zero crossing in the SR curve). Finally, an activation map for each subject was created by placing the extracted timings in the middle of the corresponding segment of a bull’s-eye plot and interpolating values between them. Results Tracking was feasible in 94% of the segments; SR curves showed a physiological pattern (Fig. 1A). For the HV, mechanical activation started from mid anteroseptal (72%) or mid inferoseptal (28%) segment at 23±5ms, spreading to basal posterolateral segment at 49±8ms from the start of QRS, in all but one case, where activation ended at basal inferoseptal segment (Fig. 1B). During CRT off, septal wall was activated 31±9ms and lateral wall 74±20ms after the beginning of QRS (p<0.01) (Fig. 1C), whereas during CRT on, septal wall was activated 41±11ms and lateral wall 38±7ms after the beginning of QRS (p=0.3) (Fig. 1D). Changing the pacing pole of the LV lead in one CRT patient also changed the start of mechanical activation in the lateral wall (Fig. 2). Conclusion Our findings comply with left ventricular activation as described in the literature and show that HFR STE could be a useful tool in defining the ablation target for arrhythmia treatment.

Role of fragmented QRS complex in the prognosis of patients undergoing cardiac resynchronization therapy. A new red flag to look for?

Abstract Introduction Cardiac resynchronization therapy (CRT) has demonstrated to reduce mortality and hospitalization for heart failure in selected patients with heart failure with reduced ejection fraction (HFrEF). However, there is a significant percentage of readmissions for heart failure (HF) after implantation. In the recent years, several biomarkers and electrocardiographic findings possibly related with prognosis in this group of patients have been identified. Fragmentation of QRS complex (fQRS) has been related with worse prognosis in various cardiac diseases, but the evidence in patients undergoing CRT is limited. Purpose The objective of this study is to evaluate if the presence of pre-implantation fragmented QRS complex has a prognostic role in patients undergoing cardiac resynchronization therapy in terms of hospitalization for HF. Methods Consecutive patients undergoing CRT were prospectively included from October 2009 to December 2022. Demographic clinical, electrocardiographic and echocardiographic variables were recorded. Prospective follow-up variables were collected from electronic clinical records and telephone interview. Fragmentation of the QRS complex was defined by the presence of different RSR′ patterns including an additional R-wave (R′), notching of the R-wave and S-wave or the presence of more than 1R′ in two contiguous leads corresponding to a main coronary artery territory. Results 244 patients were included. Mean age at the implantation of the device was 71.8 years (standard deviation, SD ±9.8 years), 79.5% were male and 40.2% were diabetic. Mean LVEF was 24.9% (SD ±8.9) and the aetiology was non-ischaemic in 50.8% of the patients and ischaemic in 49.2%. 40.2% had prior history of acute myocardial infarction. Pre-implantation fragmented QRS complex was found in 58.6% of the patients and mostly in inferior leads of the surface ECG. Mean QRS duration was 157.9ms and 82.0% had left-bundle branch block morphology. CRT with defibrillator implantation was performed in 71.4% of the patients. The median follow-up time was 27.4 month. After device implantation, mean LVEF was 33.2% and 76.6% presented NYHA class I-II. During this period, 28.7% of the patients died. Additionally, 29.1% of the patients presented at least one hospitalization for heart failure (HF), 22.5% with fQRS and 6.6% without fQRS. A multivariate survival study using Cox regression showed that the presence of pre-implantation fQRS was an independent predictor of HF hospitalization events (HR 2.24; 95% CI 1.20-4.18). Figure 1 presents Kaplan-Meier curves for hospitalization for HF. Conclusions According to our results, pre-implantation fQRS is a strong independent predictor of hospitalization for HF after CRT implantation. Thus, patients with fQRS could benefit from a more rigorous follow-up as they present higher risk of decompensation. Further research is needed to confirm our findings.Figure 1.Kaplan-Meier curves

Changes in cardiac electrical biomarker with hyperaemic stress: an experimental perspective

Abstract Background "Cardiac electrical biomarker" (CEB) is a numerical index measured by the Vectraplex ECG (vECG) System with Vectraplex AMI software that measures changes in the cardiac electrical field vectors from dipolar to multipolar during myocardial ischemia. CEB performs well in detecting NSTEMI and STEMI against physician adjudicated diagnosis. Purpose To assess changes in CEB during adenosine stress induced ischaemia. Method Thirty-three patients, in the VECTRA-PCI trial, with normal surface ECG (sECG) had CEB measured before (CEB0), at maximal hyperaemia (CEBh)) and 1-(CEB1), 2-(CEB2) and 3-(CEB3) hours after standard fractional flow reserve (FFR) assessment using intravenous adenosine. vECGs were adjudicated for quality by 2 blinded observers. vECGs with artefacts and arrhythmias were discarded and CEBs from best traces were analysed. Forty-nine individuals with non-cardiac chest pain, without past medical history or risk factors for CAD, on no medications, normal ECGs, normal blood profile acted as controls. CEBs (median, IQR) were compared using appropriate tests. Results FFR was normal (>/=0.80) (nFFR) in 25 and ischaemic (<0.80) (iFFR) in 8 patients. CEB0 in nFFR and iFFR groups were similar to each other (p=0.785) (Fig 1) and to controls (30.0; IQR 17.0-44.0, vs nFFR: p=0.057, vs iFFR: p=0.241). Compared to CEB0, CEBh was higher in nFFR (p=0.014) (Fig 1A) and iFFR (p=0.016) groups (Fig 1B). CEBh in iFFR (126.0; 109.5-216.0) higher than nFFR (44.0; 27.8-104.8), (p=0.039). In nFFR group, CEB1, 2 and 3, though numerically lower, were statistically similar to CEBh and CEB0 (Fig 1A) suggesting quick recovery. In iFFR group CEB1 was similar to and CEB2 and 3 were lower than CEBh (Fig 1B) suggesting a slower recovery of CEB. Both CEBh and change from CEB0 to CEBh (δCEB0-h), but not CEB0, predicted ischaemic FFR with similar accuracy (p=0.570) (Fig 2). CEBh >96 and δCEB0-h >28 had similar sensitivity of 87.5% with specificity of 68% and 80% respectively. Conclusion Obstructive coronary atheroma is associated with higher CEB than non-obstructive atheroma under hyperaemic stress. Both CEBh and δCEB0-h accurately predict ischaemic FFR with higher specificity of δCEB0-h. This is the first study to measure CEB changes with hyperaemic stress in patients with coronary artery disease and could have potential for wider clinical application. Figure 1. Changes in the CEB during and after hyperaemic stress in patients with normal (A) and ischaemic (B) FFR. Figure 2. Area under the ROC curve to determine the diagnostic accuracy of pre-procedural CEB, hyperaemic CEB and change in CEB from baseline to hyperaemia in determining ischaemic FFR.Fig 1. Changes in CEB with stress.Fig 2. CEB for ischaemic FFR

Abstract 17334: Association of BIN1 Deletion With Electrical and Structural Remodeling in a Transgenic BIN1 KO Mouse Model of Heart Failure-Novel Option for Effective Therapy Using VK-II-86

Introduction: Cardiac deletion of Bridging Integrator 1 (BIN1) membrane protein produces an age-related cardiomyopathy in mice. Our hypothesis was to determine whether electrical accompanies this structural remodeling and examine the utility of VK-II-86, a structural analog of carvedilol with minimum β-blocking activity, as a potential antiarrhythmic therapeutic strategy. Methods: A cardiac-specific transgenic BIN1 KO mouse was employed. Structural and electrical cardiac changes were assessed using echocardiography and EKG (Visual Sonics-Vevo Heart Image). Murine ventricular cardiomyocytes were studied using patch-clamp techniques to examine changes in ion channel function and to study the effects of VK-II-86 on the action potential (AP). Results: Loss of BIN1 (KO) significantly reduced Left Ventricular Ejection Fraction (LVEF) and Cardiac Output (CO) when compared to WT mice, with a relative reduction of nearly 20% and 35% in EF and CO, respectively. Heterozygotic mice (HET) also exhibited significant reduction in EF and CO compared to WT mice. Loss of BIN1 (KO and HET) significantly prolonged the QT interval on surface ECG by approximately 15%. This finding correlates with the increase in AP duration (APD) demonstrated in ventricular cardiomyocytes using current clamp. BIN1 deficient hearts displayed significant reduction in expression of I to , I K1 and peak I Na (80%, 40% and 20% respectively) as well as augmented expression of late I Na (50%). This electrical remodeling is likely responsible for the increased expression of early (EAD) and late (DAD) afterdepolarization observed in APs. In BIN1 deficient ventricular cardiomyocytes, the addition of 1 μM VK-II-86 prevented the development of APD prolongation and suppressed EAD and DAD development. Conclusions: Our study adds to the understanding the role of BIN1. We demonstrate the first-time electrical remodeling in the form of QT and APD prolongation associated with BIN1 deficiency, due to reduced I to and I K1 and increase in late I Na , an increase in EAD and DAD events. Additionally, VK-II-86 is shown to normalize APD in isolated cardiomyocytes and suppress afterdepolarization events, making it a potentially novel and effective therapeutic strategy in HF associated with BIN1 deficiency.

Abstract 11663: T Wave Alternans: A Clue in Plain Sight

Introduction: T-wave alternans (TWA) refers to the beat-to-beat variability in T-wave amplitudes or polarity on surface ECGs, and can signify susceptibility to malignant ventricular arrhythmias (VA). Aims: We present a case to emphasize the pathophysiology and clinical significance of this ECG finding. Case description: A 52 year-old female with history of HIV presents with shortness of breath and is treated for heart failure. In the ED, she has witnessed syncope and is found to have VT that progresses to VF. Resuscitation efforts are successful and include amiodarone loading. Figure 1A demonstrates baseline ECG on admission with a QTc of 495 ms. A few days later, an ECG reveals QTc of 696 ms with TWA (figure 1B). Shortly after, she develops polymorphic VT in the setting of long-short sequences and an R on T trigger (figure 1C) that is terminated with cardioversion. Review of pre-admission ECGs reveals that QTc prolongation occurred after initiation of a retroviral regimen that included rilpivirine and worsened with amiodarone. Both medications are discontinued, and she is eventually discharged with a QTc of 450 ms. Early theories for TWA's mechanism hypothesized that dispersion of refractoriness resulted in depolarization through alternating pathways and thus this phenomenon. Recent understanding further suggests that TWA occurs as a result of cellular alternans and variation in action potential duration due to dysregulation of repolarization. If discordant repolarization alternans ensues, whereby neighboring cells repolarize in opposite phases (long-short, short-long), the resultant repolarization gradient and heterogeneity in cellular repolarization serves as the substrate for VA; if a premature beat encounters refractory myocardium and unidirectional block occurs, a re-entrant excitation tachycardia can be initiated. Conclusions: TWA on ECG suggests myocardial electrical instability as a result of cellular repolarization inhomogeneity.

Abstract 17011: Correlation of Surface Atrial ECG Dominant Frequency to Intracardiac Atrial Electrogram Dominant Frequency

Background: The surface Atrial ECG (A-ECG) is an underused tool in persistent atrial fibrillation (PeAF) that can provide dominant frequency (DF) of atrial activation. The association between A-ECG DF and left (LA) and right atrial (RA) DF has not been established. Research Question: Does surface A-ECG DF correlate with intracardiac DF? Aims: To investigate the correlation between A-ECG peak DF and peak DF of intracardiac RA and LA electrograms (EGM) in patients with PeAF. Methods: Thirty-two patients (age 63±9 years; 71% males) with PeAF underwent 5-minute epochs of surface ECG and comprehensive LA (261.5±185.1 sites/patient) and RA (211.5±174.6 sites/patient) intracardiac mapping with 15 second recordings. The A-ECG was derived by QRST subtraction and independent component analysis filtering, and divided into overlapping10-second windows which were subjected to Fast Fourier Transform (FFT). 4 were excluded for significant artifact. A-ECG DF was calculated for each lead from the power spectrum as the average of all 10-second segments. Peak A-ECG DF was determined by regional lead location and for all 12 leads. The intracardiac EGM DF was calculated from the FFT, and peak RA and LA DF was determined. Results: A-ECG peak DF was significantly lower than intracardiac peak DF 6.08±0.64 vs 9.72±1.19 Hz, p<0.0001(LA: 9.72±1.20 Hz, p<0.0001; RA: 8.40±0.80 Hz, p<0.0001). Figure shows that A-ECG peak DF correlated with peak RA DF, r=0.77 (p<0.0001), but not with peak LA DF (r=0.31, p=0.10). Regional A-ECG lead group DF correlated with RA DF (Inferior (II, III, aVF): r=0.79, p<0.0001; Lateral (I, aVL, V5-6): r=0.78, p<0.0001; Anterior (V1-3): r=0.75, p<0.0001) but not with peak LA DF. Conclusion: Surface A-ECG DF correlates with intracardiac RA DF and not LA DF. As in atrial flutter, the RA plays a prominent role in the surface ECG manifestation of the f waves. Further study is needed to determine whether A-ECG DF can be used to identify RA versus LA drivers that may require ablation.