Surface ECG Research Articles

Mitral annular disjunction prevalence and its association with ventricular arrythmias in Upper Egypt

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Mitral annular disjunction (MAD) was first described more than 3 decades ago as an abnormal atrial displacement of the hinge point of the mitral valve away from the ventricular myocardium. MAD was associated with ventricular arrythmias and sudden cardiac death, yet some studies suggested that the presence of MAD can be potentially normal physiological function . (1) Purpose Our primary end point was assessment of the incidence of mitral annular disjunction among the cohort of mitral valve prolapse at our center and the secondary end point was the incidence and predictors of ventricular arrythmias(VAs) in our cohort. Methods It is an observational cross section study where we recruited all the patients who were diagnosed to have MAD at our center representing the area of Upper Egypt, MAD was defined as distinct separation of the mitral valve annulus and the left atrial wall and myocardial continuum, and it was initially diagnosed by the means of transthoracic echocardiography. All patients’ demographics and family history (FH) of sudden cardiac death (SCD) were collected,symptoms were assessed as regard palpitations, shortness of breathing, chest pain, pre syncope and syncope, data from echocardiography including LV internal dimensions, leaflets affection, degree of mitral regurgitation, careful ECG analysis was done extracting the data for PR interval, corrected QTc, T wave inversion, PVCs in surface ECG and in 24 hours Holter, cardiac MRI parameters including late gadolinium enhancement, its distribution and systolic curling. Results We analyzed the data of 300 patients with mitral valve prolapse, 7 % of them showed mitral annular disjunction, 33 % of the cohort were female patients, the mean age was 34 years old, the mean follow up period was 3 years, main presenting complain was palpitations with an incidence of 66 %, FH of SCD was noticed in 9 % of our cohort, Mean QRS width was 81 mseconds, mean QTc was 423 mseconds, the mean EF was 60 %, mean displacement distance was 3 mm, while the mean LA volume was 36 cm3, 80 % of the cohort showed bileaflet affection, while only 19 % of them had late gadolinium enhancement, 50 % of them had fibrosis in the papillary muscles, while systolic curling was noticed in only 9 %.VAs were defined as having premature ventricular complexes in the surface ECG or documented monomorphic ventricular tachycardia and it was noticed in 19 % of our cohort with an average burden of 10 % during a 24 hours Holter.There was a positive correlation between the FH of SCD and the Prescence of PVCs in surface ECG with a significant P value of 0.02, while there was no correlation between fibrosis and the incidence of ventricular arrythmias. Conclusions Incidence of MAD was 7 % among the MVP population at our center. Only FH of SCD was a predictor of the incidence of VAs, while ECG, echo and cardiac MRI parameters couldn`t be proved to be positively correlated with the VAs.

Outcomes of cavotricuspid isthmus-dependent fLutter ablation: randomized study comparing single vs multiple catheter procedures. The SIMPLE study

Abstract Funding Acknowledgements Type of funding sources: None. Background Catheter ablation is recommended as first-line therapy for patients with symptomatic typical atrial flutter (AFl). Although the conventional multi-catheter approach is the standard of care for cavotricuspid isthmus (CTI) ablation, a single-catheter approach was recently described as a feasible alternative. Purpose The present study sought to compare safety, efficacy, and efficiency of single vs multi-catheter approach for AFl ablation. Methods In this randomized multicentre study, consecutive patients referred for AFl ablation (n= 253) were enrolled and randomized to multiple vs single-catheter approach for CTI ablation. In the single-catheter arm CTI block was confirmed analyzing PR interval (PRI) on the surface ECG as previously described by Madaffari and colleagues: briefly, PRI defined as the time between the pacing spike and the onset of the QRS complex, was measured on the surface ECG during atrial pacing (10 V, 1.5 ms) at a stable cycle length from the tip of the ablation catheter placed at 5 o’clock (medial to CTI line), 7 o’clock (lateral to CTI line), and 9 o’clock position. CTI block was assumed when: (i) the PRI at 7 o’clock was >80ms longer than that at pacing sites of 5, and (ii) the PRI at 9 o’clock was shorter than the PRI at 7 o’clock (Figure 1). Procedural and follow-up data were collected and compared between the two arms. Results 128 and 125 patients were assigned to the single-catheter and to the multi-catheter arms, respectively. In the single-catheter arm, procedure time was singificantly shorter (37±25 vs 48±27 minutes, p=0.002), required less fluoroscopy time (430±461 vs 712±628 seconds, p<0.001) and less radiofrequency time (428±316 vs 643±519 seconds, p<0.001), achieving a higher first-pass CTI block rate [55 (45%) vs 37 (31%), p=0.044], compared with the multi-catheter arm. After a median follow-up of 12 months, 11 (4%) patients experienced AFl recurrences [5 (4%) in the single-catheter arm and 6 (5%) in the multi-catheter arm, P=0.99]. No differences were found in arrhythmia-free survival between arms (log-rank= 0.71). Results are summarized in Figure 2. Conclusions Recurrence-free survival of the single-catheter approach for typical AFl ablation is not inferior to the conventional multiple-catheter approach, reducing procedure, fluoroscopy and radiofrequency time.

A method to identify which patients will have VT substrate ablation targets prior to ablation procedure

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Dr Nanthakumar is a recipient of the Mid-career Investigator Award from the Heart & Stroke Foundation of Ontario Background Recent trials in ventricular tachycardia (VT) ablation suggest that early ablation could reduce VT burden. A method to predict which patients will have substrate ablation targets based on non-invasive testing prior to the procedure does not exist and could be of value in selecting ideal patients for early VT substrate ablation. Decrement-evoked potential (DeEP) mapping is used to identify VT substrate ablation targets.1 A method for predicting which patients would have DeEP targets on a pre-ablation 12-lead ECG has not yet been developed. Objective To develop a metric to predict the presence of physiological substrate VT ablation targets from the 12-lead ECG. Method 22 electrophysiology (EP) lab VT cases that had undergone DeEP mapping were extracted from the CARTO® 3 system and were analysed retrospectively. For each case, DeEP was calculated by subtracting last component of the nearfield evoked response in the pacing train (S1) from the latest component of the nearfield evoked decremented response of the extra stimulus (S2). By inference, 12-lead ECG prediction was calculated by subtracting the width of the 12-lead surface ECG envelope of S1 from the width of the 12-lead ECG envelope of S2. Cases were divided into three categories: - Cases displaying intracardiac DeEP between 0-10ms – no ablation targets - Cases displaying intracardiac DeEP between 10-50ms – DeEP positive - Cases displaying intracardiac DeEP >50ms – prominent DeEP present Results Out of the 22 cases, 8 were characterised as no ablation targets, 12 as DeEP positive, and 2 as prominent DeEP present. The 12-lead surface ECG measurement means were 3.5±4.6ms for the no ablation target group, 23.2±9.1ms for positive DeEP group, and 80.9±8.1ms for prominent DeEP group. The surface ECG decrement was significantly different P<0.0001 between the three groups. Consequently, we propose that ECG QRS widening of envelope width of 20ms or more may indicate the presence of DeEP targets during invasive mapping. Conclusion It may be possible to detect which patients will have substrate ablation targets based on 12-lead ECG, prior to the VT ablation procedure. Additionally, this prediction rule, based on its association with arrhythmogenic potentials, may be able to predict which ambulatory patients who have not had manifest VT, may be prone to develop VT thus help identify early VT ablation candidates. This concept should be validated in larger data sets and is ideal for training and testing using surface ECG envelopes with artificial intelligence algorithms.

Invasive electrophysiology study guided loop recorder implantation in myotonic dystrophy type 1: a prospective single-center study

Abstract Funding Acknowledgements Type of funding sources: None. Introduction In one third of the patients with myotonic dystrophy type 1 (DMT1) the cause of death is of cardiac origin. The most common cardiac manifestations are arrhythmias and conduction disturbances. Purpose Due to its extreme long monitoring properties, implantable loop recorders (ILRs) are highly suitable to detect rare cardiac arrhythmias. To date, there are only limited data using ILRs in DMT1. We aimed to evaluate the role of the invasive electrophysiology study (EPS)-guided loop recorder implantation in patients with DMT. Methods In our prospective study 18 genetically confirmed DMT1 patients underwent non-invasive cardiac examination including transthoracic echocardiography, 24-hour Holter monitoring and surface ECG. In addition, EPS was performed in all cases to evaluate the risk of sudden cardiac death and infra-Hisian conduction properties. Based on the performed non-invasive diagnostic evaluation and EPS findings, patients were divided into low, intermediate and high-risk groups. For patients with normal investigation results and normal HV interval (<55 ms) only annual cardiac follow-up visits were planned (low-risk group). Patients with increased PR interval (>240 ms), QRS duration (>120 ms), or slightly prolonged HV interval (55-70 ms) underwent implantable loop recorder (ILR) implantation (intermediate-risk group). Permanent pacemaker (PM) or implantable cardiac defibrillator (ICD) was implanted in patients with 2nd/3rd degree atrioventricular block (AVB), significantly prolonged HV interval (>100 ms) or if sustained ventricular tachyarrhythmia could be induced during EPS. All patients were followed for at least 3 years. Results According to our study criteria, 8 patients could be categorized as "intermediate risk", 7 of them received implantable loop recorder (ILR). 1 ILR had to be removed 3 weeks after implantation due to skin infarction. During three-years of follow-up, 2 patients had many asymptomatic atrial high-rate episodes, but no 2nd or 3rd degree AVB, significant asystole or malignant ventricular arrhythmia were detected. Conclusions Our single-center prospective study examined the EPS-guided ILR implantation for the risk stratification of DMT1 patients for the first time. A more extensive, multicenter study is warranted to define optimal management of DMT1 patients with slightly impaired infrahisian conduction.

Analysis of the effects of atrial pacing on the timing of left ventricular pressure rise in normal conduction and left bundle branch block

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Norwegian Research Council. Background/Introduction The timing of left ventricular pressure rise (Td) relative to QRS-onset is associated with dispersion of regional work distribution and prolongs with dyssynchrony and dyssynergistic contractions. Td is short in normal conduction and shortening of Td can be achieved with effective biventricular pacing (BIVP). The effect of atrial pacing on Td is unknown and could be important for the interpretation of Td when utilized for cardiac resynchronization therapy. Purpose We wanted to test the effects from atrial pacing (AP) compared to sinus rhythm (SR) on Td in animals with narrow QRS (nQRS) complexes and after the creation of LBBB. Methods 9 mongrel dogs were included in the study and handled according to ethics committee approved protocol/GLP. Pacing electrodes were placed epicardial on the left atrial appendage. Pressure was measured with a Micro-tip pressure sensor (Millar Inc.) in the LV and sampled at 1000Hz. LBBB was created with a retrograde placed 7F standard ablation catheter and confirmed by surface ECG and four endocardial electrodes. Td was measured from 10 consecutive beats. Mixed models were utilized for the repeated measurements. Results Analysis of the marginal means in pooled data showed that the average Td with AP was 96.7ms (95% CI: -195.7, 388.7), and in SR 96.5ms (95% CI: - 195.5, 389.0). The analysis with the Bonferroni correction for multiple comparisons revealed that the differences between pacing configurations were not statistically significant (p=0.80). The analysis revealed that AP on average lengthens Td by 0.3ms (95% confidence interval (CI): - 1.7, 2.2, p=0.8), compared to no pacing. The difference in Td in nQRS between AP and SR was 82.4ms (95% CI: 76.8, 88.1) and 82.1ms (95% CI: 76.4, 87.8) respectively (p=0.02) while the difference in Td in LBBB between AP and SR was 111.1ms (95% CI: 104.8, 117.4) and 110.9ms (95% CI: 104.581, 117.197) respectively (p=0.48). Standard deviation within 10 consecutive beats was 1.0ms (max 3.7ms, min 0.4ms, median 0.95ms), and AP did not influence Td measurement variability (p=0.53). Conclusion(s) We did not find any influence from atrial pacing in Td in this study. The significant difference between AP and SR in nQRS was extremely small and less than the sample interval of 1ms. The significance of this difference is attributed to the robustness of the Td measurement and does not represent a meaningful clinical significance. Td can be measured without being influenced by atrial pacing in both native conduction and with LBBB.

Epicardial versus endocardial pacing in cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Norwegian Research Council. Background/Introduction The timing of left ventricular pressure rise (Td) relative to QRS-onset is associated with dispersion of regional work distribution and prolongs with dyssynchrony and dyssynergistic contractions. Td is short in normal conduction and shortening of Td can be achieved with effective biventricular pacing (BIVP). The effect of endocardial compared to epicardial pacing on Td is unknown and could be important for the interpretation of Td when different pacing strategies are utilized for CRT. Purpose We wanted to analyze the measurement from QRS-onset to onset of LV pressure rise identified as the peak double derivative of LV pressure rise (Onset of Synergy, OoS) and to the peak pressure rise (Td), and test the effects of cardiac resynchronization therapy with endocardial vs epicardial pacing electrodes in a large animal model of LBBB. Methods 5 mongrel dogs were included in the study and handled according to ethics committee approved protocol/GLP. Pacing electrodes were placed epicardial on the left ventricular (LVepi) and right ventricular (RVepi) free wall, and endocardial electrodes were positioned at the right ventricular septum (RVsept) and in the LV endocardial free wall (LVendo). The atrial electrode was placed on the left atrial appendage. Pressure was measured with a Micro-tip pressure sensor (Millar Inc.) in the LV and sampled at 1000Hz. LBBB was created with a retrograde placed 7F standard ablation catheter and confirmed by surface ECG and four endocardial electrodes. Td was measured from 10 consecutive beats. Mixed models were utilized for the repeated measurements. Results Td was measured to 115±2ms at baseline in LBBB. Td decreased by 5ms from RVepi (114±3ms) to RVendo (109±3ms) regardless of LV electrode position. We then compared the effects of using LV endocardial and epicardial pacing in CRT and found that Td was 6ms higher (p<0.01) in LVepi (115±3ms) vs LVendo (109±3ms) regardless of RV electrode position. The interaction between RV RV and LV revealed that RVepi/LVendo (105±3ms) was significant shorter than RVendo/LVendo (110±3ms, p0.01) and RVepi/LVepi (115±3ms, p<0.01). OoS with RVepi/LVendo was 71±2ms, and a significant relationship between OoS and Td were found (R=0.62, p<0.01) to indicate that the myocardial contraction is affected by pacing already at 71ms after QRS-onset early during the pre-ejection period. Conclusion(s) In this study we demonstrate how endocardial and epicardial pacing applied with CRT may affect contraction patterns of the heart differently. The different effects from pacing can be measured as early as 71ms after QRS-onset. Shortening of Td occurs to a larger extent with pacing from the endocardial LV and epicardial RV, while pacing at two endocardial sites did not result in synergistic effects on Td. This may indicate that there might be an interaction between endocardial pacing sites when applied in combination.

Beat-to-beat variation of P-wave morphology immediately after ablation of persistent atrial fibrillation correlates with long-term clinical outcome

Abstract Funding Acknowledgements Type of funding sources: None. Background P-wave morphology on surface ECG reflects the atrial electrical remodelling, and is regarded as a predictor of ablation outcome for atrial fibrillation (AF). Purpose We sought to investigate whether morphological characteristics of P-waves immediately after a wide circumferential isolation of pulmonary veins (WPVI) in persistent AF (peAF) correlate with long-term maintenance of sinus rhythm (SR). Methods 33 patients (63±10 y, sustained AF 11±7 months) underwent a de-novo WPVI. A second WPVI was performed in patients with recurrent AF in order to provide complete PV disconnection. We defined "success" as patients who remained in SR after one or two procedures, and "failure" otherwise. The average duration and amplitude of the P-waves, and the coefficient of variation (CoV = standard deviation/mean) of the beat-to-beat similarity between ≥30 successive P-waves per patient were computed on ECG lead II during SR after cardioversion. Panel A shows a group of successive P-waves synchronized with regard to their centers of gravity. The similarity between the shapes of two successive synchronized P-waves was assessed using the dynamic time warping distance. Panel B shows the time-evolution of beat-to-beat distance between the P-waves displayed in Panel A. Results Over a mean follow-up of 31±9 months, 21 patients remained free from AF off antiarrhythmics (success group), while 12 patients had AF recurrence after 2 WPVIs (failure group). The clinical characteristics (e.g. age, body mass index, left atrial volume or duration in sustained AF) were similar between groups (p>0.05). The success group displayed significantly lower beat-to-beat variability of P-wave morphology than that of the failure group (p<0.05, Panel C). No significant difference was found in P-wave duration and amplitude between the two groups (p>0.05, Panel D and E). Conclusion Low P-wave beat-to-beat morphological variability immediately after WPVI for persistent AF is associated with long-term maintenance of sinus rhythm.

Delayed ventricular conduction alters ventricular repolarization in patients with heart failure: an electrocardiographic imaging study

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Personal grant from the Dutch Heart Foundation. Background In the normal human heart, the polarity of the T-wave is concordant with the QRS complex. This phenomenon is often explained by longer repolarization of earlier activated regions. Patients with delayed ventricular conduction often have discordant T-waves, but the link to regional repolarization is unknown. Aim To compare epicardial repolarization-activation (RT-AT) relations in patients with heart failure and reduced ejection fraction (HFrEF) with those having a structural normal heart. Methods 14 patients with HFrEF and delayed ventricular conduction and 11 patients no history of structural heart disease and a normal surface ECG (nQRS) were analyzed using electrocardiographic imaging (ECGI). HFrEF patients were subcategorized as left bundle branch block (LBBB, n=6) or non-specified intraventricular conduction disturbance (IVCD, n=8). Noninvasive ECGI was used to assess epicardial activation (ATs) and repolarization times (RTs). RT-AT relationships were evaluated for 24 epicardial segments using linear regression analysis. Interventricular repolarization dispersion (inter-RTD) was defined as the difference between average left-ventricular (LV) and right-ventricular RT, while total epicardial repolarization dispersion (total-RTD) was defined as the standard deviation of all epicardial RTs. The maximum of the local RT gradients (RTG) was defined as their 95th percentile. RT parameters were described as median±IQR and Kruskal Wallis tests were used to evaluate the differences between the groups. Results An HFrEF patient’s representative 24-segment AT and RT bullseyes with a positive RT-AT relation (~depolarize last, repolarize last) is provided in Figure1A. A positive RT-AT slope was present in the majority of HFrEF patients (1.14±0.17 for LBBB and 1.16±0.55 for IVCD), whereas the nQRS group (-0.25±2.16) demonstrated an overall slightly negative slope with high variability (Figure 1B and 1C). Individual (thin lines) and group-averaged (thick lines) RT-AT slopes normalized for the earliest AT and earliest RT (in case of a positive RT-AT slope) or latest RT (in case of a negative slope) are visualized in Figure 1C. Both inter-RTD (41±25 for LBBB, 32±13 ms for IVCD, and 8±20 ms for nQRS) as well as total-RTD (34±9for LBBB, 34±12 ms for IVCD, and 24±8 ms for nQRS) was significantly higher in the LBBB and IVCD group compared to the nQRS group, whereas RTG did not differ between the groups (Figure 1B). RT-AT slopes, inter-RTD, total-RTD, and RTG did not significant differ between the LBBB and IVCD subgroup. Conclusion This ECGI study shows that in patients with HFrEF, later activated regions also have a later completion of repolarization, regardless of conduction delay, whereas a variable RT-AT relation is present in subjects with structural normal hearts. HFrEF additionally initiates a higher degree of interventricular and total repolarization dispersion.

Comparison of myocardial depolarization spreading after resynchronization with left bundle branch area pacing versus biventricular pacing

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Left bundle branch area pacing (LBBAP) is an emerging new method of cardiac resynchronization therapy (CRT) in patients with left bundle branch block (LBBB). Studies comparing LBBAP with standard biventricular pacing (BiV) have shown similar post-operative shortening of QRS duration and left ventricular activation times. Calculation of equivalent dipole (ED) trajectories from 12-lead high-resolution ECG (hrECG) provides additional insight into myocardial depolarization and may be used for further assessment of left ventricular activation. Purpose The aim of this study was to determine myocardial depolarization patterns with assessment of ED trajectories in patients undergoing CRT with LBBAP or BiV and to compare them to myocardial depolarization patterns of healthy controls. Methods Twenty-five heart failure patients in sinus rhythm and LBBB with indication for CRT were randomized in LBBAP or BiV pacing group. Five-minute supine 12-lead hrECG recordings before and one month after implantation were assessed. LBBAP group was compared to BiV group and both groups were compared to the control of healthy subjects with normal surface ECG. The QRS duration was measured manually by two independent electrophysiologists and averaged. ED trajectories were constructed with the use of inverse algorithm method. The length of ED trajectory was defined as a line between the start and the end of the ED trajectory and its orientation with azimuth and elevation angles. (Figure 1). Results Eleven patients received LBBAP and 14 BiV. There were no differences in baseline characteristics (72% male, 64% non-ischemic cardiomyopathy) between groups. The average baseline QRS duration was 174±20 ms in LBBAP and 180±17 ms in BiV group (p=0.42). QRS duration decreased to 134±14 ms after LBBAP (p<0.01) and 137±11 ms after BiV pacing (p<0.01) and was comparable in both groups (p=0.59). There was also no difference in absolute (p=0.72) or relative (p=0.72) QRS shortening. The absolute and relative ED shortening did not differ (p=0.43 and p=0.38, respectively). At follow-up, analysis of ED trajectories showed a significant difference in elevation angle in both groups (p<0.01). The elevation angle in LBBAP group (6±30°) was significantly different from the angle in BiV group (-44±33°) (p < 0.01), pointing more toward apex of the heart (Figure 2). Furthermore, elevation angle in LBBAP was more similar (absolute difference 49°) to healthy subjects than the elevation angle in BiV group (absolute difference 103°) (p<0.01). There was no intergroup difference in azimuth angle (p=0.07). Conclusion Compared to BiV pacing, resynchronization with LBBAP produces significantly different ED trajectory orientation, which was more comparable to orientation in healthy controls. While both resynchronization methods result in similar QRS narrowing, LBBAP may provide more physiological depolarization of the left ventricle in comparison to BiV.

Generation of cardiac digital twins based on noninvasive cardiac mapping

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Generalitat Valenciana Grants Ministerio de Ciencia, Innovación y Universidades Background Personalized cardiac digital twins have been proposed as a clinical tool to plan ablation strategies during cardiac arrhythmias. However, these personalization frameworks normally rely on invasive recordings which limits their clinical applicability. Electrocardiographic Imaging (ECGI) is a mapping technique that allows the reconstruction of global cardiac activity non-invasively. Purpose Evaluate the applicability of ECGI as a non-invasive tool for the planification of ablation strategies based on personalized digital twins. Methods Cardiac digital twins generated from endocardial or ECGI mapping were compared in a patient with Atrial Flutter prescribed for cardiac ablation. Endocardial mapping was obtained in the right atrium by using electroanatomical mappings. ECGI was recorded during the ablation procedure with a mapping system of 128 body surface recordings. For the cardiac digital twin based on endocardial mapping, the reentrant circuit around the tricuspid valve was reproduced based on the activation time maps obtained with the electroanatomical mapping system. Total activation time of both atria was personalized based on the duration of the F-waves on the ECG since the left atrium was not endocardialy mapped. For the cardiac digital twin based on the ECGI, activation times obtained in both left and right atrium were used to set-up the personalized model. From both approaches, computed torso potentials were calculated. The correlation with real body surface recordings was compared. To further evaluate the fidelity of the models, the efficacy of the ablation strategy performed on the real patient was evaluated over the digital twins. Results Both digital twins, the one based on endocardial mapping, and the one based on ECGI were compared. Regarding dynamics of the model, both models reproduced the reentrant circuit around the tricuspid valve. Interestingly, only the ECGI digital twin reproduced a reentrant wave around the right pulmonary veins. When endocardial map was used for the personalization, a median conduction velocity (CV) of 90.5 cm/s was obtained for the right atrium and 174.7 cm/s for the left; whereas when ECGI was used, the median CV were 104.2 cm/s at the right and 129.1 cm/s at the left atrium. The ability to reproduce body surface ECGs of both digital twins demonstrated that the one based on endocardial mapping obtained a low correlation of 0.13, whereas the ECGI digital twin increase the correlation up to 0.66. Regarding the ablation outcome, ablation terminated the arrhythmia only in the cardiac digital twin based on ECGI. Conclusion The possibility to generate cardiac digital twins based on non-invasive ECGI mapping has been demonstrated. This opens the door to obtaining personalized cardiac digital twins before endocardial interventions which can be used to plan ablation procedures.

Standard and extended electrocardiographic screening for the subcutaneous implantable cardioverter-defibrillator

Abstract Funding Acknowledgements Type of funding sources: None. Background The subcutaneous implantable cardioverter-defibrillator (SICD) is effective therapy for sudden cardiac death prevention. The condition for implantation is an electrocardiographic screening test before procedure (ECG-s). Patients who don’t pass are regarded to be at risk of inappropriate detection of tachyarrhythmias with inappropriate interventions. A patient is considered suitable for implant if at least one surface ECG lead (sense vector) is acceptable for all tested postures. Objective The aim of the study was to identify the incidence of failure, the predicting factors and clinical importance of extended ECG-s with right sided lead position and lying on the left and right side of the body. Methods ECG-s to determine suitability for SICD is based and performed using a manufacturer –specific measurement tool. We performed this test in 75 consecutive pts with indication for SICD therapy on the basis of standard manufacturer protocol(lead at the left sternum border: sitting, standing and lying position), and extended for right sternal lead location and two additional body position: lying on the left and right side (10 position for each individual). We analyzed: age, gender, body mass index(BMI), heart rate, heart rhythm(sinus/atrial fibrillation), QRS duration, PR interval, corrected QT interval(QTc), echocardiography parameters, etiology. Results ECG-s failure occurred in 6/75(8%) of patients. Screening results: 1 vector failure rate with the standard device and lead positions: primary(P) 12%, seconadary(S) 17%, alternative(A) 40%, P vs. A and S vs. A p<0,001. Testing with an electrode positioned on the right sternum border- 1 vector failure: (P) 10%,seconadary(S) 17%, alternative(A) 48%, P vs. A and S vs. A p<0,001. In case of failure on left side 50%, 14% and 6% of pts passed the test with the right sided lead position for P, S and A vector respectively, p<0.001. Identified factors predicting ESG-s passing vs. failure included: QTc interval 445,32±35,4 vs. 480,6±37,6 ms for any vector(p=0,034), BMI:26,7±4,7 vs. 29,9±4,7 for vector A( p=0,008 ), EF: 43,3±20,1 vs. 34,0±16,2 for vector A( p=0,027). Sense vector failure rate with the left sternal lead location lying on the left and right side of the body was concordant with the rate lying on the back, p=0,05. For the right parasternal lead location the rate failure was lower lying on the right side for all sense vectors: P, S and A(p=0,045; 0,083 and 0,020) respectively. Conclusions ECG screening failure rate for SICD is comparable with previous reports. The right sternal lead location screening is effective and enables important clinical findings before implantation and in case of lead reposition( defibrillation threshold test failure) during procedure. We recommend to screen routinely on both sternum borders. Some additional body position testing: lying on the left and right side of the body, mimicking sleeping/rest could be an important element to determine eligibility for SICD.

Marked first-degree AV block may lead to complete AV block development

Abstract Funding Acknowledgements Type of funding sources: None. Background First-degree atrioventricular (AV) block (PR interval >200 ms) is considered a benign condition with rare progression to a higher degree AV block. The site of block is determined with electrophysiological (EP) study and measurement of His-ventricular (HV) interval, with normal values below 55 ms. Prolonged HV interval > 70 ms is predictive of higher-grade AV block development. Marked first-degree AV block with a PR > 300 ms may lead to symptoms such as fatigue, poor exercise tolerance and palpitations. When symptoms are correlated to the conduction delay, permanent pacemaker (PPM) implantation to restore AV synchrony should be considered. In the Framingham heart study, patients with first-degree AV block had a threefold higher risk of PPM implantation. However, there is no data on the HV intervals and the rate of progression of conduction disorder in patients with marked first-degree AV block. Purpose To assess the predictive value of HV interval measurement in patients with marked first-degree AV block for progression to a higher-degree conduction disorder. Methods We prospectively evaluated consecutive patients with symptomatic marked first-degree AV block that underwent a PPM implantation. His electrograms were recorded during the implantation, and HV intervals were measured from the first deflection of the His signal to the earliest onset of ventricular activation on a 12-lead surface ECG. Patients were followed for 6 months with three out-patient visits, during which the PPM was temporarily inhibited to check for intrinsic AV conduction. Results Seventeen patients were evaluated between January 2020 and September 2022. Ten patients (59%) were male, and 7 (41%) were female, with an average age of 61 ± 19 years. All patients had markedly prolonged PR interval (383 ± 47 ms) and narrow QRS complex (100 ± 16 ms). Three patients (17%) had intermittent type 1 second-degree AV block, right bundle branch block was recorded in two (12%) and left anterior fascicular block in four (24%) patients. Except for one patient with a corrected atrial septal defect, there were no echocardiographic signs of structural heart disease with a left ventricular ejection fraction of 61 ± 5%. The HV intervals were on the upper limit of normal values at 54 ± 6ms and no patient had an HV interval above 70 ms. Two patients (12%) developed complete AV block during follow-up: one female, and one male, 28 and 83 years old, respectively, with a PR interval 392 and 363 ms, QRS 104 and 94 ms, and HV 57 and 48 ms. None of the two had any additional conduction blocks at the time of PPM implant. Conclusion In our cohort of patients with symptomatic first-degree AV block (PR>300 ms), two patients (12%) developed complete AV block despite normal HV intervals at the time of implant. Closer monitoring, beyond only EP measurements, of patients with markedly prolonged PR intervals is warranted for the potential progression of conduction disorder.

Long term conservation of electrical synchrony by multipoint pacing with dynamic atrioventricular delays

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Abbott. Introduction Automatic adjustment of atrioventricular delay (AVD) with SyncAV has been shown to improve electrical synchronization. However, the long term effects of SyncAV optimization on electrical synchrony are unknown. Purpose Evaluate the effect of SyncAV programming on 6-month (6mo) QRS duration during biventricular (BiV) and left ventricle only MultiPoint Pacing (MPP). Methods Patients with LBBB and QRS duration (QRSd) ≥ 150 ms scheduled for CRT-P/D device implantation with quadripolar LV lead were enrolled in this prospective study. QRSd was measured post-implant from 12-lead surface ECG by blinded experts during the following pacing modes: intrinsic conduction, MPP (MPP=RV+LV1+LV2) and LV-only MPP (LVMPP=LV1+LV2). For each mode, SyncAV was enabled (e.g. MPP+SyncAV) with the patient-tailored SyncAV offset that minimized QRSd. Patients were then randomized 1:1 to receive MPP+SyncAV or LVMPP+SyncAV with the optimal offset identified at implant, and QRSd was re-evaluated at the 6mo follow-up. Results Fifty-nine patients (72% male, 41% ischemic, 26% ejection fraction, 166 ms intrinsic QRSd) completed device implant and QRSd assessment. Relative to intrinsic conduction at implant, the MPP+SyncAV group (n=30) had a QRSd reduction of 26% at implant (162 to 122 ms, p<0.001), and 20% at 6mo (162 to 130 ms, p<0.001). The LVMPP+SyncAV group (n=29) had a QRSd reduction of 24% at implant (165 to 128 ms, p<0.001), and 15% at 6mo (165 to 140 ms, p<0.001). In the MPP+SyncAV group, 28/30 (93%) of patients had more than 10% reduction in QRSd with respect to intrinsic at implant, with 27/30 (90%) maintaining this trend at 6 mo follow up. With LVMPP+SyncAV pacing, only 25/29 (86%) of patients had more than 10% reduction in QRSd with respect to intrinsic at implant, and this reduced to 18/29 (62%) maintaining this trend at 6 mo follow up. Conclusion MPP combined with SyncAV significantly improved acute electrical synchrony at implant in CRT patients with LBBB, as assessed by QRSd reduction. Significant QRSd reduction was maintained at 6 months post-implant by both biventricular and LV-only MPP configurations.

P266 SUBCUTANEOUS DEFIBRILLATOR USE LIMITATION IN PATIENT AFFECT BY ARRHITMOGENIC CARDIOMYOPATHY IN REAL WORLD

Abstract Introduction The prevention of sudden cardiac death (SCD) through the implantation of a defibrillator (ICD) represents one of the fundamental milestones in the management of arrhythmogenic cardiomyopathy (ACM). Individual characteristics of the patient and of the disease can help in the selection of the device [transvenous (TV) or subcutaneous (S–ICD) defibrillator]. The objective of this study is to evaluate the major factors limiting S–ICD implantation in a real–world ACM patient population. Methods This multicenter retrospective observational study enrolled consecutive patients undergoing ICD implantation in primary or secondary prevention for ACM at the participating centers. The population was subdivided according to the execution of the preimplant S–ICD screening test and its result. Baseline clinical and instrumental data were analyzed to identify predictors of passing the screening test. Results 21 ACM patients (67% men) who underwent 24 S–ICD or TV–ICD implant procedures were enrolled. 70.8% of patients (N=17) were screened for S–ICD. Screening was not performed in 4 patients (17%): in one case due to an indication for resynchronization therapy and in three patients because they were implanted in the pre–S–ICD era. Screening failed in 53% of cases. The cause of the failures were the low voltages of the QRS (100% of the failures) and a poor stability of the trace in the different positions tested for significant variation of the QRS/T ratio (37.5% of the failures). No significant difference was noted between the clinical and instrumental characteristics of the two subgroups (Table 1), although the patients who passed the screening showed a trend towards a greater QRS amplitude in DI (0.52±0.29 vs 0.28±0.17 mV – P= 0.07) and to present a positive QRS in DI (100% vs 50%; P=0.08 – Table 2). Conclusions The use of the S–ICD in patients with ACM could be limited by some intrinsic characteristics of the disease. In a real–world cohort of patients affected by ACM, the presence of low QRS voltages on the surface ECG and positional morphology variations allowed S–ICD use in half of the patient candidates.

P182 A STRANGE ELECTROCARDIOGRAM RECORDED AFTER A FALL TO THE GROUND

Abstract An 84–year–old man was found unconscious on the ground by his daughter. The patient had a medical history of arterial hypertension, dyslipidemia and type II diabetes mellitus complicated by peripheral neuropathy and has been experiencing frequent falls. The emergency services were alerted, and the man was taken to the emergency room. In the ER, an abnormal electrocardiogram was recorded, and an urgent cardiological consultation was requested. Upon reading the ECG, the cardiologist ordered the patient‘s body temperature to be measured, which was found to be 29.7°C. The recorded ECG showed signs of severe hypothermia, including an advanced atrioventricular block (in this case, III–degree AV block), a widening of the QRS complex with the appearance of the Osborn wave, and a prolonged QT interval. The Osborn wave is a positive deflection visible at the J point and it is an uncommon electrocardiographic finding that immediately suggests hypothermia, although it is not pathognomonic (it can also be found in acute myocardial ischemia, hypercalcemia, sepsis, and other non–hypothermic conditions). The electrophysiological basis of the Osborn wave lies in the Ito current, a transient current caused by the release of potassium ions from the ventricular myocardiocyte, which is responsible for a brief partial repolarization during phase 1 of the action potential. Hypothermia increases the amplitude and width of the action potential notch due to the Ito current in the epicardium much more than in the endocardium, creating a transmural voltage gradient that manifests on the surface ECG as the Osborn wave. The Osborn wave is initially more evident in the inferolateral leads; as the body temperature decreases, the wave gradually becomes visible in all 12 leads and, when the body temperature returns to normal, the wave progressively disappears. This potential difference also correlates with possible proarrhythmic effects and, when linked to acute myocardial ischemia, the Osborn wave is an adverse prognostic factor as it is associated with a higher risk of ventricular fibrillation. In this case, the patient had fallen during the night and remained on the ground for hours. He was hospitalized for short intensive observation, warmed up, and hydrated, with a rapid and complete resolution of the clinical and electrocardiographic abnormalities

P163 THE ELECTROCARDIOGRAPHIC CHANGES ASSOCIATED WITH HYPOTHERMIA: THE OSBORN WAVE

Abstract A 93–year–old patient came to our observation for general malaise, sensory obnubilation, aphasia and dysphagia. He had arterial hypertension in drug treatment. At the first medical contact, the body temperature was 28 °C. The ECG showed a non–evaluable atrial activity (likely atrial paralysis) with the presence of a junctional rhythm at the frequency of 37 bpm. Blood pressure was around 100/60 mmHg with preserved cardiovascular compensation, in the presence of a moderately depressed cardiac function. Furthermore, the presence of a positive deflection in the terminal part of the QRS complex with elevation of the point J, in the precordial lateral leads V4–V6, and a terminal slowing of the QRS complex in the inferior leads, the so–called ‘wave of Osborn’, were also observed Figure 1. Given the reduction of the sensory, the patient was subjected to brain CT scan with finding of a thin hyperdense layer around the right and left hemispheric convexity suggestive for subdural haematoma. After adequate warming and supportive therapy, a progressive increase in heart rate was observed with restoration of the sinus rhythm and disappearance of the Osborn wave, Figure 2. The Osborn wave is the most specific electrocardiographic sign of hypothermia. It consists of an electrocardiographic deflection which is manifested as a late delta wave or as a small r ’wave following the QRS. It is the manifestation on the surface ECG of the electric gradient between a more prominent spike and dome action potential of epicardial cells than that of endocardial cells, an effect that is believed to be linked to a slowing down of the kinetics of activation of K þ channels Ito compared to calcium channels, associated with low temperature. This wave is not specific for hypothermia but can also occur in other clinical conditions such as subarachnoid haemorrhage, myocardial ischaemia, acidosis, in the presence of hypercalcemia, early repolarization and even in normal subjects. Its amplitude also tends to increase in conjunction with the reduction in body temperature. The bradyarrhythmias and conduction disorders associated with hypothermia cease spontaneously with an increase in body temperature, so the use of beta stimulating drugs and the insertion of transvenous pacemakers, the latter for the mechanical irritation effect on the endocardium, should be considered with caution due to the high risk of inducing ventricular tachyarrhythmias and ventricular fibrillation.

Individualized QT interval (QTi) is a powerful diagnostic tool in long QT syndrome: results from a large validation study.

Diagnosis of Long QT syndrome (LQTS) is based on prolongation of the QT interval corrected for heart rate (QTc) on surface ECG and genotyping. However, up to 25% of genotype positive patients have a normal QTc interval. We recently showed that individualized QT interval (QTi) derived from 24 h holter data and defined as the QT value at the intersection of an RR interval of 1,000 ms with the linear regression line fitted through QT-RR data points of each individual patient was superior over QTc to predict mutation status in LQTS families. This study aimed to confirm the diagnostic value of QTi, fine-tune its cut-off value and evaluate intra-individual variability in patients with LQTS. From the Telemetric and Holter ECG Warehouse, 201 recordings from control individuals and 393 recordings from 254 LQTS patients were analysed. Cut-off values were obtained from ROC curves and validated against an in house LQTS and control cohort. ROC curves indicated very good discrimination between controls and LQTS patients with QTi, both in females (AUC 0.96) and males (AUC 0.97). Using a gender dependent cut-off of 445 ms in females and 430 ms in males, a sensitivity of 88% and specificity of 96% were achieved, which was confirmed in the validation cohort. No significant intra-individual variability in QTi was observed in 76 LQTS patients for whom at least two holter recordings were available (483 ± 36 ms vs. 489 ± 42 ms, p = 0.11). This study confirms our initial findings and supports the use of QTi in the evaluation of LQTS families. Using the novel gender dependent cut-off values, a high diagnostic accuracy was achieved.

CE-454610-2 STEREOTACTIC ARRHYTHMIA RADIOABLATION IN VENTRICULAR FIBRILLATION WITH LEFT VENTRICULAR THROMBUS

Stereotactic arrhythmia radioablation (STAR) has been studied for management of refractory ventricular tachycardia (VT) that is not amenable to traditional catheter ablation. We present the case of a patient with recurrent ventricular tachycardia (VT) and left ventricular (LV) thrombus successfully treated with STAR therapy. A 48-year-old man with morbid obesity, paroxysmal atrial fibrillation and infarct related cardiomyopathy was admitted with late presentation of new anterolateral ST elevation myocardial infarction complicated by cardiogenic shock, managed with mechanical circulatory support. He was found to have a 3 x 2.7 cm thrombus in the LV apex (Panel A). He underwent successful percutaneous intervention to an acute left anterior descendinig coronary artery occlusion. During hospitalization, despite aggressive measures, he was noted to have polymorphic ventricular tachycardia (VT), triggered by premature ventricular contractions (PVCs) arising from his LV apical infarct (Panel B). He was treated with multiple antiarrhythmic medications (amiodarone, lidocaine) in addition to electrolyte repletion but unfortunately required repeated external defibrillation for PVC induced VF (Panel C). A dual chamber implantable cardioverter-defibrillator was placed and despite overdrive pacing, he suffered from recurrent life-threatening VT and ventricular fibrillation (VF) requiring additional defibrillation (Panel D). Because he was not a candidate for endocardial ablation, orthotopic heart transplantation, and was deemed too unstable for epicardial ablation, the decision was made to pursue STAR. Surface ECG and 4D computed tomography (Panel E) were used to localize the focus of the VT trigger. A single dose of 25 Gray of radiation was delivered to the LV apex. Our patient has been free of ventricular arrhythmias for 14 months. There has been no clinical evidence of early or late toxicity related to radiotherapy thus far. In challenging cases of PVC induced VT and VF not amenable to traditional therapies, such as our patient, STAR may offer a therapeutic option. Further studies are required.

PO-03-226 MACHINE LEARNING IDENTIFIES FEATURES OF ARRHYTHMOGENIC QRS FRAGMENTATION IN HUMAN CARDIOMYOPATHY: IMPLICATIONS FOR IMPROVING AND AUTOMATING RISK STRATIFICATION

Slow, heterogeneous ventricular activation can provide the substrate for reentrant ventricular arrhythmias (VA), but its manifestation on the surface ECG as a risk stratifier is not well-defined beyond the presence of QRS duration (QRSd) >120ms or QRS fragmentation (fQRS). Our aim was to use machine learning (ML) to characterize the spatiotemporal features of QRS fragmentation that best predict VA in patients with cardiomyopathy (CM). Prospectively enrolled ischemic and non-ischemic CM patients with prophylactic defibrillators (n=95) underwent digital, high-resolution 12-lead ECG recordings for 5-minutes during intrinsic rhythm. Abnormal intra QRS peaks in the signal-averaged precordial leads (V1-V6) were identified using our previously validated time-domain algorithm. For each spatial location (V1-V6), QRS peak characteristics including width, amplitude and relative temporal location within the QRS were transformed into 4-bin histograms. Random forest models of the QRS peak counts and characteristics in each lead were trained on groups of 76 patients and tested on groups of 19 patients with stratified repeated random subsampling cross-validation to determine the features that predicted VA outcome. QRS peak counts and characteristics were additionally modelled with QRSd and other relevant clinical characteristics. CM patients (age 62±11 yrs, male 85%, LVEF 27±7%, ischemic etiology 62%) were followed for 24 (15-43) months and 22% had VA (+VA). QRSd was longer in +VA than -VA (135±25 vs. 114±26ms, p=0.001), but age, LVEF, CM etiology and fQRS were similar. The individual ML models determined (ROCAUC) QRS peak count (0.87), width (0.88) and location (0.84) to be predictors of VA (Table). In these models, the features most predictive of VA were a greater peak count in V1, a greater # of peaks less <6.25% of the QRSd in V1 and a greater # of peaks in the final quarter of the QRS of V1 (Figure). ML models of peak amplitude, QRSd and fQRS were not predictive of VA. The addition of clinical variables to the QRS peak count, width and location models did not improve VA prediction. Arrhythmogenic ventricular substrate can be independently identified during intrinsic rhythm by QRS fragmentation in V1 characterized by either a greater total # of peaks, a greater # of very narrow peaks, or a greater # of peaks at the end of the QRS according to our ML model. These findings require external validation and may improve risk stratification in defibrillator-eligible CM patients.Tabled 1Table. Performance of Random Forest ML Model.ModelROC [95% CI]Prespecified SensitivitySpecificityPPVNPVF1-ScoreQRS duration0.57 [0.35-0.87]90%0.220.270.490.42Qualitative fQRS0.56 [0.33-0.73]90%0.120.240.350.38All clinical characteristics∗0.46 (0.22-0.70]90%0.220.260.930.41QRS peak characteristics- Total Count0.87 [0.65-1.00]90%0.640.501.000.64- Width0.88 [0.70-1.00]90%0.730.541.000.69- Amplitude0.66 [0.36-0.93]90%0.250.290.710.44- Temporal Location in QRS0.84 [0.66-1.00]90%0.630.471.000.62QRS peak + clinical characteristics*- Total Count0.79 [0.55-0.97]90%0.560.421.000.57- Width0.82 [0.58-0.97]90%0.630.451.000.61- Amplitude0.68 [0.42-0.93]90%0.360.320.960.48- Temporal Location in QRS0.76 [0.52-0.95]90%0.530.391.000.55Age, Sex, Cardiomyopathy, QRS duration, Heart Rate, LVEF, NYHA Class, Comorbidities and Cardiac Medications Open table in a new tab

BS-452757-4 ANTI-ARRHYTHMIC EFFECTS OF ANDROGEN DEPRIVATION THERAPIES IN A SCN5A LOSS-OF-FUNCTION MOUSE MODEL

Sex is a major determinant of the incidence and clinical presentation in arrhythmia syndromes such as Brugada syndrome (BrS). We generated a novel SCN5A-G1408R/+ knock-in mouse model mimicking key features of human BrS regarding male predominance and susceptibility to ventricular tachycardias. This study aimed to explore the effect and molecular mechanisms of androgen deprivation on cardiac arrhythmogenicity in a mouse model of BrS. Animals were studied using surface ECG with and without flecainide challenge (10 mg/kg body weight), telemetric recordings, molecular, biochemical as well as histological analyses. To study the effect of antiandrogenic treatments on the rhythmogenic state and its influence on transcriptional alterations of cardiac ion channel genes, male G1408R/+ mice were either chronically treated with the androgen receptor (AR) blocker flutamide by subcutaneously implanted osmotic pumps or orchiectomized. Sex-dependent analysis showed that 81% (25/31 animals) of male G1408R/+ and only 14% (2/14 animals) of their female littermates developed flecainide-induced polymorphic ventricular tachycardias (VT). Only male G1408R/+ mice, previously 100% inducible for VT underwent androgen deprivation (flutamide for 4 weeks vs. orchiectomy). The arrhythmogenic phenotype was rescued in both groups of antiandrogenic therapy. VT incidence in the flutamide group was reduced to 13% (2/16), while VT in the orchiectomy group declined to 33% (3/9). At baseline, (untreated) male G1408R/+ mice exhibited reduced cardiac expression of NaV1.5 protein compared to male wild type (wt) mice, particularly in the right ventricular myocardium. Treatment with flutamide for 4 weeks resulted in increased NaV1.5 expression in male G1408R/+ mice to levels similar to male wt mice. Interestingly, orchiectomized G1408R/+ mice revealed levels of NaV1.5 protein even higher compared to wt mice, which were particularly abundant in the right ventricular free wall. We observed a significant anti-arrhythmic effect induced by androgen deprivation in the G1408R/+ mouse model mimicking human BrS. Our data indicate that the anti-arrhythmic effect is potentially driven by increasing right ventricular NaV1.5 membrane expression as a result of anti-androgenic treatment.