Automatic and interpretable prediction of the site of origin in outflow tract ventricular arrhythmias: machine learning integrating electrocardiograms and clinical data.

The treatment of outflow tract ventricular arrhythmias (OTVA) through radiofrequency ablation requires the precise identification of the site of origin (SOO). Pinpointing the SOO enhances the likelihood of a successful procedure, reducing intervention times and recurrence rates. Current clinical methods to identify the SOO are based on qualitative analysis of pre-operative electrocardiograms (ECG), heavily relying on physician's expertise. Although computational models and machine learning (ML) approaches have been proposed to assist OTVA procedures, they either consume substantial time, lack interpretability or do not use clinical information. Here, we propose an alternative strategy for automatically predicting the ventricular origin of OTVA patients using ML. Our objective was to classify ventricular (left/right) origin in the outflow tracts (LVOT and RVOT, respectively), integrating ECG and clinical data from each patient. Extending beyond differentiating ventricle origin, we explored specific SOO characterization. Utilizing four databases, we also trained supervised learning models on the QRS complexes of the ECGs, clinical data, and their combinations. The best model achieved an accuracy of 89%, highlighting the significance of precordial leads V1-V4, especially in the R/S transition and initiation of the QRS complex in V2. Unsupervised analysis revealed that some origins tended to group closer than others, e.g., right coronary cusp (RCC) with a less sparse group than the aortic cusp origins, suggesting identifiable patterns for specific SOOs.

Personalized pulmonary vein isolation with very high-power short-duration lesions guided by left atrial wall thickness: the QDOT-by-LAWT randomized trial.

AIMS: Pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) using very high-power short-duration (vHPSD) radiofrequency (RF) ablation proved to be safe and effective. However, vHPSD applications result in shallower lesions that might not be always transmural. Multidetector computed tomography-derived left atrial wall thickness (LAWT) maps could enable a thickness-guided switching from vHPSD to the standard-power ablation mode. The aim of this randomized trial was to compare the safety, the efficacy, and the efficiency of a LAWT-guided vHPSD PVI approach with those of the CLOSE protocol for PAF ablation (NCT04298177). METHODS AND RESULTS: Consecutive patients referred for first-time PAF ablation were randomized on a 1:1 basis. In the QDOT-by-LAWT arm, for LAWT ≤2.5 mm, vHPSD ablation was performed; for points with LAWT > 2.5 mm, standard-power RF ablation titrating ablation index (AI) according to the local LAWT was performed. In the CLOSE arm, LAWT information was not available to the operator; ablation was performed according to the CLOSE study settings: AI ≥400 at the posterior wall and ≥550 at the anterior wall. A total of 162 patients were included. In the QDOT-by-LAWT group, a significant reduction in procedure time (40 vs. 70 min; P < 0.001) and RF time (6.6 vs. 25.7 min; P < 0.001) was observed. No difference was observed between the groups regarding complication rate (P = 0.99) and first-pass isolation (P = 0.99). At 12-month follow-up, no significant differences occurred in atrial arrhythmia-free survival between groups (P = 0.88). CONCLUSION: LAWT-guided PVI combining vHPSD and standard-power ablation is not inferior to the CLOSE protocol in terms of 1-year atrial arrhythmia-free survival and demonstrated a reduction in procedural and RF times.

Scar architecture affects the electrophysiological characteristics of induced ventricular arrhythmias in hypertrophic cardiomyopathy.

AIMS: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) detects myocardial scarring, a risk factor for ventricular arrhythmias (VAs) in hypertrophic cardiomyopathy (HCM). The LGE-CMR distinguishes core, borderzone (BZ) fibrosis, and BZ channels, crucial components of re-entry circuits. We studied how scar architecture affects inducibility and electrophysiological traits of VA in HCM. METHODS AND RESULTS: We correlated scar composition with programmed ventricular stimulation-inducible VA features using LGE intensity maps. Thirty consecutive patients were enrolled. Thirteen (43%) were non-inducible, 6 (20%) had inducible non-sustained, and 11 (37%) had inducible sustained mono (MMVT)- or polymorphic VT/VF (PVT/VF). Of 17 induced VA, 13 (76%) were MMVT that either ended spontaneously, persisted as sustained monomorphic, or degenerated into PVT/VF. Twenty-seven patients (90%) had LGE. Of these, 17 (57%) had non-sustained or sustained inducible VA. Scar mass significantly increased (P = 0.002) from non-inducible to inducible non-sustained and sustained VA patients in both the BZ and core components. Borderzone channels were found in 23%, 67%, and 91% of non-inducible, inducible non-sustained, and inducible sustained VA patients (P = 0.003). All 13 patients induced with MMVT or monomorphic-initiated PVT/VF had LGE. The origin of 10/13 of these VTs matched scar location, with 8/10 of these LGE regions showing BZ channels. During follow-up (20 months, interquartile range: 7-37), one patient with BZ channels and inducible PVT had an ICD shock for VF. CONCLUSION: Scar architecture determines inducibility and electrophysiological traits of VA in HCM. Larger studies should explore the role of complex LGE patterns in refining risk assessment in HCM patients.

Functional mapping to reveal slow conduction and substrate progression in atrial fibrillation.

AIMS: The aim of our study was to analyse the response to short-coupled atrial extrastimuli to identify areas of hidden slow conduction (HSC) and their relationship with the atrial fibrillation (AF) phenotype. METHODS AND RESULTS: Twenty consecutive patients with paroxysmal AF and persistent AF (10:10) underwent the first pulmonary vein isolation procedure. Triple short-coupled extrastimuli were delivered in sinus rhythm (SR), and the evoked response was analysed: sites exhibiting double or highly fragmented electrograms (EGM) were defined as positive for HSC (HSC+). The delta of the duration of the bipolar EGM was analysed, and bipolar EGM duration maps were built. High-density maps were acquired using a multipolar catheter during AF, SR, and paced rhythm. Spatial co-localization of HSC+ and complex fractionated atrial EGMs (CFAE) during AF was evaluated. Persistent AF showed a higher number and percentage of HSC+ than paroxysmal AF (13.9% vs. 3.3%, P < 0.001). The delta of EGM duration was 53 ± 22 ms for HSC+ compared with 13 ± 11 (10) ms in sites with negative HSC (HSC-) (P < 0.001). The number and density of HSC+ were lower than CFAE during AF (19 vs. 56 per map, P < 0.001). The reproducibility and distribution of HSC+ in repeated maps were superior to CFAE (P = 0.19 vs. P < 0.001). Sites with negative and positive responses showed a similar bipolar voltage in the preceding sinus beat (1.65 ± 1.34 and 1.48 ± 1.47 mV, P = 0.12). CONCLUSION: Functional mapping identifies more discrete and reproducible abnormal substrates than mapping during AF. The HSC+ sites in response to triple extrastimuli are more frequent in persistent AF than in paroxysmal AF.

Assessing left atrial intramyocardial fat infiltration from computerized tomography angiography in patients with atrial fibrillation.

AIMS: Epicardial adipose tissue might promote atrial fibrillation (AF) in several ways, including infiltrating the underlying atrial myocardium. However, the role of this potential mechanism has been poorly investigated. The aim of this study is to evaluate the presence of left atrial (LA) infiltrated adipose tissue (inFAT) by analysing multi-detector computer tomography (MDCT)-derived three-dimensional (3D) fat infiltration maps and to compare the extent of LA inFAT between patients without AF history, with paroxysmal, and with persistent AF. METHODS AND RESULTS: Sixty consecutive patients with AF diagnosis (30 persistent and 30 paroxysmal) were enrolled and compared with 20 age-matched control; MDCT-derived images were post-processed to obtain 3D LA inFAT maps for all patients. Volume (mL) and mean signal intensities [(Hounsfield Units (HU)] of inFAT (HU -194; -5), dense inFAT (HU -194; -50), and fat-myocardial admixture (HU -50; -5) were automatically computed by the software. inFAT volume was significantly different across the three groups (P = 0.009), with post-hoc pairwise comparisons showing a significant increase in inFAT volume in persistent AF compared to controls (P = 0.006). Dense inFAT retained a significant difference also after correcting for body mass index (P = 0.028). In addition, more negative inFAT radiodensity values were found in AF patients. Regional distribution analysis showed a significantly higher regional distribution of LA inFAT at left and right superior pulmonary vein antra in AF patients. CONCLUSION: Persistent forms of AF are associated with greater degree of LA intramyocardial adipose infiltration, independently of body mass index. Compared to controls, AF patients present higher LA inFAT volume at left and right superior pulmonary vein antra.

Clinical impact of aging on outcomes of cardioneuroablation for reflex syncope or functional bradycardia: Results from the cardionEuroabLation: patiEnt selection, imaGe integrAtioN and outComEs-The ELEGANCE multicenter study.

BACKGROUND: Cardioneuroablation (CNA) is a novel treatment for reflex syncope. The effect of aging on CNA efficacy is not fully understood. OBJECTIVE: The purpose of this study was to assess the impact of aging on candidacy and efficacy of CNA for treating vasovagal syncope (VVS), carotid sinus syndrome (CSS), and functional bradyarrhythmia. METHODS: The ELEGANCE (cardionEuroabLation: patiEnt selection, imaGe integrAtioN and outComEs) multicenter study assessed CNA in patients with reflex syncope or severe functional bradyarrhythmia. Patients underwent pre-CNA Holter electrocardiography (ECG), head-up tilt testing (HUT), and electrophysiological study. CNA candidacy and efficacy was assessed in 14 young (18-40 years), 26 middle-aged (41-60 years), and 20 older (>60 years) patients. RESULTS: Sixty patients (37 men; mean age 51 ± 16 years) underwent CNA. The majority (80%) had VVS, 8% had CSS, and 12% had functional bradycardia/atrioventricular block. Pre-CNA Holter ECG, HUT, and electrophysiological findings did not differ across age groups. Acute CNA success was 93%, without differences between age groups (P = .42). Post-CNA HUT response was negative in 53%, vasodepressor in 38%, cardioinhibitory in 7%, and mixed in 2%, without differences across age groups (P = .59). At follow-up (8 months, interquartile range 4-15), 53 patients (88%) were free of symptoms. Kaplan-Meier curves did not show differences in event-free survival between age groups (P = .29). The negative predictive value of a negative HUT was 91.7%. CONCLUSION: CNA is a viable treatment for reflex syncope and functional bradyarrhythmia in all ages, and is highly effective in mixed VVS. HUT is a key step in postablation clinical assessment.

Personalized pulmonary vein antrum isolation guided by left atrial wall thickness for persistent atrial fibrillation.

AIMS: Pulmonary vein (PV) antrum isolation proved to be effective for treating persistent atrial fibrillation (PeAF). We sought to investigate the results of a personalized approach aimed at adapting the ablation index (AI) to the local left atrial wall thickness (LAWT) in a cohort of consecutive patients with PeAF. METHODS AND RESULTS: Consecutive patients referred for PeAF first ablation were prospectively enrolled. The LAWT three-dimensional maps were obtained from pre-procedure multidetector computed tomography and integrated into the navigation system. Ablation index was titrated according to the local LAWT, and the ablation line was personalized to avoid the thickest regions while encircling the PV antrum. A total of 121 patients (69.4% male, age 64.5 ± 9.5 years) were included. Procedure time was 57 min (IQR 50-67), fluoroscopy time was 43 s (IQR 20-71), and radiofrequency (RF) time was 16.5 min (IQR 14.3-18.4). The median AI tailored to the local LAWT was 387 (IQR 360-410) for the anterior wall and 335 (IQR 300-375) for the posterior wall. First-pass PV antrum isolation was obtained in 103 (85%) of the right PVs and 103 (85%) of the left PVs. Median LAWT values were higher for PVs without first-pass isolation as compared to the whole cohort (P = 0.02 for left PVs and P = 0.03 for right PVs). Recurrence-free survival was 79% at 12 month follow-up. CONCLUSION: In this prospective study, LAWT-guided PV antrum isolation for PeAF was effective and efficient, requiring low procedure, fluoroscopy, and RF time. A randomized trial comparing the LAWT-guided ablation with the standard of practice is in progress (ClinicalTrials.gov, NCT05396534).

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

BACKGROUND: Catheter ablation is recommended as first-line therapy for patients with symptomatic typical 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. The present study sought to compare safety, efficacy, and efficiency of single vs. multi-catheter approach for atrial flutter (AFl) ablation. METHODS: In this randomized multi-center 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, PR interval (PRI) on the surface ECG was used to prove CTI block. 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 significantly shorter (37 ± 25 vs. 48 ± 27 minutes, p = 0.002) and 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). CONCLUSIONS: The single-catheter approach for typical AFl ablation is not inferior to the conventional multiple-catheter approach, reducing procedure, fluoroscopy, and radiofrequency time.

Reproducibility analysis of the computerized tomography angiography-derived left atrial wall thickness maps.

BACKGROUND: Adapting the ablation index (AI) to the left atrial wall thickness (LAWT) derived from computed tomography angiography (CTA) allows for a personalized approach that showed to improve PVI safety and outcomes. METHODS: Three observers with different degrees of experience performed complete LAWT analysis of CTA for 30 patients and repeated the analysis for 10 of these patients. Intra- and inter-observer reproducibility of these segmentations was assessed. RESULTS: Geometric congruence of repeated reconstruction of LA endocardial surface showed that 99.4% of points in the 3D reconstructed mesh were within < 1 mm distance for the intra-observer variability and 95.1% for the inter-observer. For the LA epicardial surface, an 82.4% of points were within < 1 mm for intra-observer and a 77.7% for inter-observer. A 1.99% of points were further than 2 mm for the intra-observer and a 4.1% for the inter-observer. Colour agreement between LAWT maps showed that a 95.5% and a 92.9% intra- and inter-observer respectively presented the same colour or a change to the colour immediately above or below. The ablation index (AI), which was adapted to this LAWT colour maps to perform a personalized pulmonary vein isolation (PVI), showed an average difference in the derived AI lower than 25 units in all cases. For all analyses, the concordance increased with user-experience. CONCLUSION: Geometric congruence of LA shape was high, for both endocardial and epicardial segmentations. LAWT measurements were reproducible, increasing with user experience. This translated into a negligible impact in the target AI.

A hybrid clinical and electrocardiographic score to predict the origin of outflow tract ventricular arrhythmias.

BACKGROUND: To predict the outflow tract ventricular arrhythmias (OTVA) site of origin (SOO) before the ablation procedure has important practical implications. The present study sought to prospectively evaluate the accuracy of a clinical and electrocardiographic hybrid algorithm (HA) for the prediction of OTVAs-SOO, and at the same time to develop and to prospectively validate a new score with improved discriminatory capacity. METHODS: In this multicenter study, we prospectively enrolled consecutive patients referred for OTVA ablation (N = 202), and we divided them in a derivation sample and a validation cohort. Surface ECGs during OTVA were analyzed to compare previous published ECG-only criteria and to develop a new score. RESULTS: In the derivation sample (N = 105), the correct prediction rate of HA and ECG-only criteria ranged from 74 to 89%. R-wave amplitude in V3 was the best ECG parameter for discriminating LVOT origin in V3 precordial transition (V3PT) patients, and was incorporated to the novel weighted hybrid score (WHS). WHS correctly classified 99 (94.2%) patients, presenting 90% sensitivity and 96% specificity (AUC 0.97) in the entire population; WHS mantained a 87% sensitivity and 91% specificity (AUC 0.95) in patients with V3PT subgroup. The high discriminatory capacity was confirmed in the validation sample (N = 97): the WHS exhibited an AUC (0.93), and a WHS ≥ 2 allowed a correct prediction of LVOT origin in 87 (90.0%) cases, yielding a sensitivity of 87% and specificity of 90%; moreover, the V3PT subgroup showed an AUC of 0.92, and a punctuation ≥ 2 predicted an LVOT origin with a sensitivity of 94% and specificity of 78%. CONCLUSIONS: The novel hybrid score has proved to accurately anticipate the OTVA's origin, even in those with a V3 precordial transition. A Weighted hybrid score. B Typical examples of the use of the weighted hybrid score. C ROC analysis of WHS and previous ECG criteria for prediction of LVOT origin in the derivation cohort. D ROC analysis of WHS and previous ECG criteria for prediction of LVOT origin in the V3 precordial transition OTVA subgroup.

Preventive substrate ablation in chronic post-myocardial infarction patients with high-risk scar characteristics for ventricular arrhythmias: rationale and design of PREVENT-VT study.

BACKGROUND: Recent studies showed that an early strategy for ventricular tachycardia (VT) ablation resulted in reduction of VT episodes or mortality. Cardiac magnetic resonance (CMR)-derived border zone channel (BZC) mass has proved to be a strong non-invasive predictor of VT in post-myocardial infarction (MI). CMR-guided VT substrate ablation proved to be safe and effective for reducing sudden cardiac death (SCD) and VA occurrence. METHODS: PREVENT-VT is a prospective, randomized, multicenter, and controlled trial designed to evaluate the safety and efficacy of prophylactic CMR-guided VT substrate ablation in chronic post-MI patients with CMR-derived arrhythmogenic scar characteristics. Chronic post-MI patients with late gadolinium enhancement (LGE) CMR will be evaluated. CMR images will be post-processed and the BZC mass measured: patients with a BZC mass > 5.15 g will be eligible. Consecutive patients will be enrolled at 3 centers and randomized on a 1:1 basis to undergo a VT substrate ablation (ABLATE arm) or optimal medical treatment (OMT arm). Primary prevention ICD will be implanted following guideline recommendations, while non-ICD candidates will be implanted with an implantable cardiac monitor (ICM). The primary endpoint is a composite outcome of sudden cardiac death (SCD) or sustained monomorphic VT, either treated by an ICD or documented with ICM. Secondary endpoints are procedural safety and efficiency outcomes of CMR-guided ablation. DISCUSSION: In some patients, the first VA episode causes SCD or severe neurological damage. The aim of the PREVENT-VT is to evaluate whether primary preventive substrate ablation may be a safe and effective prophylactic therapy for reducing SCD and VA occurrence in patients with previous MI and high-risk scar characteristics based on CMR. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04675073, registered on January 1, 2021.

Relationship between the posterior atrial wall and the esophagus: esophageal position and temperature measurement during atrial fibrillation ablation (AWESOME-AF). A randomized controlled trial.

BACKGROUND: Pulmonary vein isolation (PVI) implies unavoidable ablation lesions to the left atrial posterior wall, which is closely related to the esophagus, leading to several potential complications. This study evaluates the usefulness of the esophageal fingerprint in avoiding temperature rises during paroxysmal atrial fibrillation (PAF) ablation. METHODS: Isodistance maps of the atrio-esophageal relationship (esophageal fingerprint) were derived from the preprocedural computerized tomography. Patients were randomized (1:1) into two groups: (1) PRINT group, the PVI line was modified according to the esophageal fingerprint; (2) CONTROL group, standard PVI with operator blinded to the fingerprint. The primary endpoint was temperature rise detected by intraluminal esophageal temperature probe monitoring. Ablation settings were as specified on the Ablate BY-LAW study protocol. RESULTS: Sixty consecutive patients referred for paroxysmal AF ablation were randomized (42 (70%) men, mean age 60 ± 11 years). Temperature rise (> 39.1 °C) occurred in 5 (16%) patients in the PRINT group vs. 17 (56%) in the CONTROL group (p < 0.01). Three AF recurrences were documented at a mean follow-up of 12 ± 3 months (one (3%) in the PRINT group and 2 (6.6%) in the CONTROL group, p = 0.4). CONCLUSION: The esophageal fingerprint allows for a reliable identification of the esophageal position and its use for PVI line deployment results in less frequent esophageal temperature rises when compared to the standard approach. Further studies are needed to evaluate the impact of PVI line modification to avoid esophageal heating on long-term outcomes. The development of new imaging-derived tools could ultimately improve patient safety (NCT04394923).

Relationship between the posterior atrial wall and the esophagus: Esophageal position during atrial fibrillation ablation.

Background: Atrial fibrillation ablation implies a risk of esophageal thermal injury. Esophageal position can be analyzed with imaging techniques, but evidence for esophageal mobility is inconsistent. Objectives: The purpose of this study was to analyze esophageal position stability from one procedure to another and during a single procedure. Methods: Esophageal position was compared in 2 patient groups. First, preprocedural multidetector computerized tomography (MDCT) of first pulmonary vein isolation and redo intervention (redo group) was segmented with ADAS 3D™ to compare the stability of the atrioesophageal isodistance prints. Second, 3 imaging modalities were compared for the same procedure (multimodality group): (1) preprocedural MDCT; (2) intraprocedural fluoroscopy obtained with the transesophageal echocardiographic probe in place with CARTOUNIVU™; and (3) esophageal fast anatomic map (FAM) at the end of the procedure. Esophageal position correlation between different imaging techniques was computed in MATLAB using semiautomatic segmentation analysis. Results: Thirty-five redo patients were analyzed and showed a mean atrioesophageal distance of 1.2 ± 0.6 mm and a correlation between first and redo procedure esophageal fingerprint of 91% ± 5%. Only 3 patients (8%) had a clearly different position. The multi-imaging group was composed of 100 patients. Esophageal position correlation between MDCT and CARTOUNIVU was 82% ± 10%; between MDCT and esophageal FAM was 80% ± 12%; and between esophageal FAM and CARTOUNIVU was 83% ± 15%. Conclusion: There is high stability of esophageal position between procedures and from the beginning to the end of a procedure. Further research is undergoing to test the clinical utility of the esophageal fingerprinted isodistance map to the posterior atrial wall.