Regional conduction velocities determined by noninvasive mapping are associated with arrhythmia-free survival after atrial fibrillation ablation.

BACKGROUND: Atrial arrhythmogenic substrate is a key determinant of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI), and reduced conduction velocities have been linked to adverse outcome. However, a noninvasive method to assess such electrophysiologic substrate is not available to date. OBJECTIVE: This study aimed to noninvasively assess regional conduction velocities and their association with arrhythmia-free survival after PVI. METHODS: A consecutive 52 patients scheduled for AF ablation (PVI only) and 19 healthy controls were prospectively included and received electrocardiographic imaging (ECGi) to noninvasively determine regional atrial conduction velocities in sinus rhythm. A novel ECGi technology obviating the need of additional computed tomography or cardiac magnetic resonance imaging was applied and validated by invasive mapping. RESULTS: Mean ECGi-determined atrial conduction velocities were significantly lower in AF patients than in healthy controls (1.45 ± 0.15 m/s vs 1.64 ± 0.15 m/s; P < .0001). Differences were particularly pronounced in a regional analysis considering only the segment with the lowest average conduction velocity in each patient (0.8 ± 0.22 m/s vs 1.08 ± 0.26 m/s; P < .0001). This average conduction velocity of the "slowest" segment was independently associated with arrhythmia recurrence and better discriminated between PVI responders and nonresponders than previously proposed predictors, including left atrial size and late gadolinium enhancement (magnetic resonance imaging). Patients without slow-conduction areas (mean conduction velocity <0.78 m/s) showed significantly higher 12-month arrhythmia-free survival than those with 1 or more slow-conduction areas (88.9% vs 48.0%; P = .002). CONCLUSION: This is the first study to investigate regional atrial conduction velocities noninvasively. The absence of ECGi-determined slow-conduction areas well discriminates PVI responders from nonresponders. Such noninvasive assessment of electrical arrhythmogenic substrate may guide treatment strategies and be a step toward personalized AF therapy.

Personalized voltage maps guided by cardiac magnetic resonance in the era of high-density mapping.

BACKGROUND: Voltage mapping could identify the conducting channels potentially responsible for ventricular tachycardia (VT). Standard thresholds (0.5-1.5 mV) were established using bipolar catheters. No thresholds have been analyzed with high-density mapping catheters. In addition, channels identified by cardiac magnetic resonance (CMR) has been proven to be related with VT. OBJECTIVE: The purpose of this study was to analyze the diagnostic yield of a personalized voltage map using CMR to guide the adjustment of voltage thresholds. METHODS: All consecutive patients with scar-related VT undergoing ablation after CMR (from October 2018 to December 2020) were included. First, personalized CMR-guided voltage thresholds were defined systematically according to the distribution of the scar and channels. Second, to validate these new thresholds, a comparison with standard thresholds (0.5-1.5 mV) was performed. Tissue characteristics of areas identified as deceleration zones (DZs) were recorded for each pair of thresholds. In addition, the relation of VT circuits with voltage channels was analyzed for both maps. RESULTS: Thirty-two patients were included [mean age 66.6 ± 11.2 years; 25 (78.1%) ischemic cardiomyopathy]. Overall, 52 DZs were observed: 44.2% were identified as border zone tissue with standard cutoffs vs 75.0% using personalized voltage thresholds (P = .003). Of the 31 VT isthmuses detected, only 35.5% correlated with a voltage channel with standard thresholds vs 74.2% using adjusted thresholds (P = .005). Adjusted cutoff bipolar voltages that better matched CMR images were 0.51 ± 0.32 and 1.79 ± 0.71 mV with high interindividual variability (from 0.14-1.68 to 0.7-3.21 mV). CONCLUSION: Personalized voltage CMR-guided personalized voltage maps enable a better identification of the substrate with a higher correlation with both DZs and VT isthmuses than do conventional voltage maps using fixed thresholds.

Post-Ablation cardiac Magnetic resonance to assess Ventricular Tachycardia recurrence (PAM-VT study).

AIMS: Conducting channels (CCs) detected by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) are related to ventricular tachycardia (VT). The aim of this work was to study the ability of post-ablation LGE-CMR to evaluate ablation lesions. METHODS AND RESULTS: This is a prospective study of consecutive patients referred for a scar-related VT ablation. LGE-CMR was performed 6-12 months prior to ablation and 3-6 months after ablation. Scar characteristics of pre- and post-ablation LGE-CMR were compared. During the study period (March 2019-April 2021), 61 consecutive patients underwent scar-related VT ablation after LGE-CMR. Overall, 12 patients were excluded (4 had poor-quality LGE-CMR, 2 died before post-ablation LGE-CMR, and 6 underwent post-ablation LGE-CMR 12 months after ablation). Finally, 49 patients (age: 65.5 ± 9.8 years, 97.9% male, left ventricular ejection fraction: 34.8 ± 10.4%, 87.7% ischaemic cardiomyopathy) were included. Post-ablation LGE-CMR showed a decrease in the number (3.34 ± 1.03 vs. 1.6 ± 0.2; P < 0.0001) and mass (8.45 ± 1.3 vs. 3.5 ± 0.6 g; P < 0.001) of CCs. Arrhythmogenic CCs disappeared in 74.4% of patients. Dark core was detected in 75.5% of patients, and its presence was not related to CC reduction (52.2 ± 7.4% vs. 40.8 ± 10.6%, P = 0.57). VT recurrence after one year follow-up was 16.3%. The presence of two or more channels in the post-ablation LGE-CMR was a predictor of VT recurrence (31.82% vs. 0%, P = 0.0038) with a sensibility of 100% and specificity of 61% (area under the curve 0.82). In the same line, a reduction of CCs < 55% had sensibility of 100% and specificity of 61% (area under the curve 0.83) to predict VT recurrence. CONCLUSION: Post-ablation LGE-CMR is feasible, and a reduction in the number of CCs is related with lower risk of VT recurrence. The dark core was not present in all patients. A decrease in VT substrate was also observed in patients without a dark core area in the post-ablation LGE-CMR.

Myocardial scarring and recurrence of ventricular arrhythmia in patients surviving an out-of-hospital cardiac arrest.

INTRODUCTION: Prediction of recurrent ventricular arrhythmia (VA) in survivors of an out-of-hospital cardiac arrest (OHCA) is important, but currently difficult. Risk of recurrence may be related to presence of myocardial scarring assessed with late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Our study aims to characterize myocardial scarring as defined by LGE-CMR in survivors of a VA-OHCA and investigate its potential role in the risk of new VA events. METHODS: Between 2015 and 2022, a total of 230 VA-OHCA patients without ST-segment elevation myocardial infarction had CMR before implantable cardioverter-defibrillator implantation for secondary prevention at Copenhagen University Hospital, Rigshospitalet, and Hospital Clínic, University of Barcelona, of which n = 170 patients had a conventional (no LGE protocol) CMR and n = 60 patients had LGE-CMR (including LGE protocol). Scar tissue including core, border zone (BZ) and BZ channels were automatically detected by specialized investigational software in patients with LGE-CMR. The primary endpoint was recurrent VA. RESULTS: After exclusion, n = 52 VA-OHCA patients with LGE-CMR and a mean left ventricular ejection fraction of 49 ± 16% were included, of which 18 (32%) patients reached the primary endpoint of VA. Patients with recurrent VA in exhibited greater scar mass, core mass, BZ mass, and presence of BZ channels compared with patients without recurrent VA. The presence of BZ channels identified patients with recurrent VA with 67% sensitivity and 85% specificity (area under the ROC curve (AUC) 0.76; 95% CI: 0.63-0.89; p < .001) and was the strongest predictor of the primary endpoint. CONCLUSIONS: The presence of BZ channels was the strongest predictor of recurrent VA in patients with an out of-hospital cardiac arrest and LGE-CMR.

Magnetic resonance detection of advanced atrial cardiomyopathy increases the risk for atypical atrial flutter occurrence following atrial fibrillation ablation.

AIMS: Recurrence of arrhythmia after catheter ablation of atrial fibrillation (AF) in the form of atypical atrial flutter (AFL) is common among a significant number of patients and often requires redo ablation with limited success rates. Identifying patients at high risk of AFL after AF ablation could aid in patient selection and personalized ablation approach. The study aims to assess the relationship between pre-existing atrial cardiomyopathy and the occurrence of AFL following AF ablation. METHODS AND RESULTS: We analysed a cohort of 1007 consecutive AF patients who underwent catheter ablation and were included in a prospective registry. Patients who did not have baseline cardiac magnetic resonance imaging and late gadolinium enhancement (LGE-CMR) or did not experience any recurrences were excluded. A total of 166 patients were included gathering 56 patients who underwent re-ablation due to AFL recurrences and 110 patients who underwent re-ablation due to AF recurrences (P = 0.11). A multiparametric assessment of atrial cardiomyopathy was based on basal LGE-CMR, including left atrial (LA) volume, LA sphericity, and global and segmental LA fibrosis using semiautomated post-processing software. Out of the initial cohort of 1007 patients, AFL and AF occurred in 56 and 110 patients, respectively. An age higher than 65 [odds ratio (OR) = 5.6, 95% confidence interval (CI): 2.2-14.4], the number of previous ablations (OR = 3.0, 95% CI: 1.2-7.8), and the management of ablation lines in the index procedure (OR = 2.5, 95% CI: 1.0-6.3) were independently associated with AFL occurrence. Furthermore, several characteristics assessed by LGE-CMR were identified as independent predictors of AFL recurrence after the index ablation for AF, such as enhanced LA sphericity (OR = 1.3, 95% CI: 1.1-1.6), LA global fibrosis (OR = 1.03, 95% CI: 1.01-1.07), and increased fibrosis in the lateral wall (OR = 1.03, 95% CI: 1.01-1.04). CONCLUSION: Advanced atrial cardiomyopathy assessed by LGE-CMR, such as increased LA sphericity, global LA fibrosis, and fibrosis in the lateral wall, is independently associated with arrhythmia recurrence in the form of AFL following AF ablation.

Evolution of Deceleration Zones During Ventricular Tachycardia Ablation and Relation With Cardiac Magnetic Resonance.

BACKGROUND: A new functional mapping strategy based on targeting deceleration zones (DZs) has become one of the most commonly used strategies within the armamentarium of substrate-based ablation methods for ventricular tachycardia (VT) in patients with structural heart disease. The classic conduction channels detected by voltage mapping can be accurately determined by cardiac magnetic resonance (CMR). OBJECTIVES: The purpose of this study was to analyze the evolution of DZs during ablation and their correlation with CMR. METHODS: Forty-two consecutive patients with scar-related VT undergoing ablation after CMR in Hospital Clinic (October 2018-December 2020) were included (median age 65.3 ± 11.8 years; 94.7% male; 73.7% ischemic heart disease). Baseline DZs and their evolution in isochronal late activation remaps were analyzed. A comparison between DZs and CMR conducting channels (CMR-CCs) was realized. Patients were prospectively followed for VT recurrence for 1 year. RESULTS: Overall, 95 DZs were analyzed, 93.68% of which were correlated with CMR-CCs: 44.8% located in the middle segment and 55.2% located in the entrance/exit of the channel. Remapping was performed in 91.7% of patients (1 remap: 33.3%, 2 remaps: 55.6%, and 3 remaps: 2.8%). Regarding the evolution of DZs, 72.2% disappeared after the first ablation set, with 14.13% not ablated at the end of the procedure. A total of 32.5% of DZs in remaps correlated with a CMR-CCs already detected, and 17.5% were associated with an unmasked CMR-CCs. One-year VT recurrence was 22.9%. CONCLUSIONS: DZs are highly correlated with CMR-CCs. In addition, remapping can lead to the identification of hidden substrate initially not identified by electroanatomic mapping but detected by CMR.

Stepwise application of ECG and electrogram-based criteria to ensure electrical resynchronization with left bundle branch pacing.

AIMS: To define a stepwise application of left bundle branch pacing (LBBP) criteria that will simplify implantation and guarantee electrical resynchronization. Left bundle branch pacing has emerged as an alternative to biventricular pacing. However, a systematic stepwise criterion to ensure electrical resynchronization is lacking. METHODS AND RESULTS: A cohort of 24 patients from the LEVEL-AT trial (NCT04054895) who received LBBP and had electrocardiographic imaging (ECGI) at 45 days post-implant were included. The usefulness of ECG- and electrogram-based criteria to predict accurate electrical resynchronization with LBBP were analyzed. A two-step approach was developed. The gold standard used to confirm resynchronization was the change in ventricular activation pattern and shortening in left ventricular activation time, assessed by ECGI. Twenty-two (91.6%) patients showed electrical resynchronization on ECGI. All patients fulfilled pre-screwing requisites: lead in septal position in left-oblique projection and W paced morphology in V1. In the first step, presence of either right bundle branch conduction delay pattern (qR or rSR in V1) or left bundle branch capture Plus (QRS ≤120 ms) resulted in 95% sensitivity and 100% specificity to predict LBBP resynchronization, with an accuracy of 95.8%. In the second step, the presence of selective capture (100% specificity, only 41% sensitivity) or a spike-R <80 ms in non-selective capture (100% specificity, sensitivity 46%) ensured 100% accuracy to predict resynchronization with LBBP. CONCLUSION: Stepwise application of ECG and electrogram criteria may provide an accurate assessment of electrical resynchronization with LBBP (Graphical abstract).

Predictive value of late gadolinium enhancement cardiovascular magnetic resonance in patients with persistent atrial fibrillation: dual-centre validation of a standardized method.

Aims: With recurrence rates up to 50% after pulmonary vein isolation (PVI) in persistent atrial fibrillation (AF), predictive tools to improve patient selection are needed. Patient selection based on left atrial late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has been proposed previously (UTAH-classification). However, this approach has not been widely established, in part owed to the lack of standardization of the LGE quantification method. We have recently established a standardized LGE-CMR method enabling reproducible LGE-quantification. Here, the ability of this method to predict outcome after PVI was evaluated. Methods and results: This dual-centre study (n = 219) consists of a prospective derivation cohort (n = 37, all persistent AF) and an external validation cohort (n = 182; 66 persistent, 116 paroxysmal AF). All patients received an LGE-CMR prior to first-time PVI-only ablation. LGE was quantified based on the signal-intensity-ratio relative to the blood pool, applying a uniform LGE-defining threshold of >1.2.  In patients with persistent AF in the derivation cohort, left atrial LGE-extent above a cut-off value of 12% was found to best predict relevant low-voltage substrate (≥2 cm two with <0.5 mV during sinus rhythm) and arrhythmia-free survival 12 months post-PVI. When applied to the external validation cohort, this cut-off value was also predictive of arrhythmia-free survival for both, the total cohort and the subgroup with persistent AF (LGE < 12%: 80% and 76%; LGE > 12%: 55% and 44%; P = 0.007 and P = 0.029, respectively). Conclusion: This dual-centre study established and validated a standardized, reproducible LGE-CMR method discriminating PVI responders from non-responders, which may improve choice of therapeutic approach or ablation strategy for patients with persistent AF.

Non-invasive assessment of pulmonary vein isolation durability using late gadolinium enhancement magnetic resonance imaging.

AIMS: Electrical reconnection of pulmonary veins (PVs) is considered an important determinant of recurrent atrial fibrillation (AF) after pulmonary vein isolation (PVI). To date, AF recurrences almost automatically trigger invasive repeat procedures, required to assess PVI durability. With recent technical advances, it is becoming increasingly common to find all PVs isolated in those repeat procedures. Thus, as ablation of extra-PV targets has failed to show benefit in randomized trials, more and more often these highly invasive procedures are performed only to rule out PV reconnection. Here we aim to define the ability of late gadolinium enhancement (LGE)-magnetic resonance imaging (MRI) to rule out PV reconnection non-invasively. METHODS AND RESULTS: This study is based on a prospective registry in which all patients receive an LGE-MRI after AF ablation. Included were all patients that-after an initial PVI and post-ablation LGE-MRI-underwent an invasive repeat procedure, which served as a reference to determine the predictive value of non-invasive lesion assessment by LGE-MRI.: 152 patients and 304 PV pairs were analysed. LGE-MRI predicted electrical PV reconnection with high sensitivity (98.9%) but rather low specificity (55.6%). Of note, LGE lesions without discontinuation ruled out reconnection of the respective PV pair with a negative predictive value of 96.9%, and patients with complete LGE lesion sets encircling all PVs were highly unlikely to show any PV reconnection (negative predictive value: 94.4%). CONCLUSION: LGE-MRI has the potential to guide selection of appropriate candidates and planning of the ablation strategy for repeat procedures and may help to identify patients that will not benefit from a redo-procedure if no ablation of extra-PV targets is intended.

Conduction System Pacing vs Biventricular Pacing in Heart Failure and Wide QRS Patients: LEVEL-AT Trial.

BACKGROUND: Conduction system pacing (CSP) has emerged as an alternative to biventricular pacing (BiVP). Randomized studies comparing both therapies are scarce and do not include left bundle branch pacing. OBJECTIVES: This study aims to compare ventricular resynchronization achieved by CSP vs BiVP in patients with cardiac resynchronization therapy indication. METHODS: LEVEL-AT (Left Ventricular Activation Time Shortening with Conduction System Pacing vs Biventricular Resynchronization Therapy) was a randomized, parallel, controlled, noninferiority trial. Seventy patients with cardiac resynchronization therapy indication were randomized 1:1 to BiVP or CSP, and followed up for 6 months. Crossover was allowed when primary allocation procedure failed. Primary endpoint was the change in left ventricular activation time, measured using electrocardiographic imaging. Secondary endpoints were left ventricular reverse remodeling and the combined endpoint of heart failure hospitalization or death at 6-month follow-up. RESULTS: Thirty-five patients were allocated to each group. Eight (23%) patients crossed over from CSP to BiVP; 2 patients (6%) crossed over from BiVP to CSP. Electrocardiographic imaging could not be performed in 2 patients in each group. A similar decrease in left ventricular activation time was achieved by CSP and BiVP (-28 ± 26 ms vs -21 ± 20 ms, respectively; mean difference -6.8 ms; 95% CI: -18.3 ms to 4.6 ms; P < 0.001 for noninferiority). Both groups showed a similar change in left ventricular end-systolic volume (-37 ± 59 mL CSP vs -30 ± 41 mL BiVP; mean difference: -8 mL; 95% CI: -33 mL to 17 mL; P = 0.04 for noninferiority) and similar rates of mortality or heart failure hospitalizations (2.9% vs 11.4%, respectively) (P = 0.002 for noninferiority). CONCLUSIONS: Similar degrees of cardiac resynchronization, ventricular reverse remodeling, and clinical outcomes were attained by CSP as compared to BiVP. CSP could be a feasible alternative to BiVP. (LEVEL-AT [Left Ventricular Activation Time Shortening With Conduction System Pacing vs Biventricular Resynchronization Therapy]; NCT04054895).

Conduction system pacing vs. biventricular pacing in patients with ventricular dysfunction and AV block.

BACKGROUND: It is unknown whether His-Purkinje conduction system pacing (HPCSP), as either His bundle or left bundle branch pacing, could be an alternative to cardiac resynchronization therapy (BiVCRT) for patients with left ventricular dysfunction needing ventricular pacing due to atrioventricular block. The aim of the study is to compare the echocardiographic response and clinical improvement between HPCSP and BiVCRT. METHODS: Consecutive patients who successfully received HPCSP were compared with a historical cohort of BiVCRT patients. Patients were 1:1 matched by age, LVEF, atrial fibrillation, renal function and cardiomyopathy type. Responders were defined as patients who survived, did not require heart transplantation and increased LVEF ≥5 points at 6-month follow-up. RESULTS: HPCSP was successfully achieved in 92.5% (25/27) of patients. During follow-up, 8% (2/25) of HPCSP patients died and 4% (1/25) received a heart transplant, whereas 4% (1/25) of those in the BiVCRT cohort died. LVEF improvement was 10% ± 8% HPCSP versus 7% ± 5% BiVCRT (p = .24), and the percentage of responders was 76% (19/25) HPCSP versus 64% (16/25) BiVCRT (p = .33). Among survivors, the percentage of patients who improved from baseline II-IV mitral regurgitation (MR) to 0-I MR was 9/11 (82%) versus 2/8 (25%) (p = .02). Compared to those with BiVCRT, patients with HPCSP achieved better NYHA improvement: 1 point versus 0.5 (OR 0.34; p = .02). CONCLUSION: HPCSP in patients with LVEF ≤45% and atrioventricular block improved the LVEF and induced a response similar to that of BiVCRT. HPCSP significantly improved MR and NYHA functional class. HPCSP may be an alternative to BiVCRT in these patients. (Figure 1. Central Illustration). [Figure: see text].

Septal flash correction with His-Purkinje pacing predicts echocardiographic response in resynchronization therapy.

BACKGROUND: His-Purkinje conduction system pacing (HPCSP) has been proposed as an alternative to Cardiac Resynchronization Therapy (CRT); however, predictors of echocardiographic response have not been described in this population. Septal flash (SF), a fast contraction and relaxation of the septum, is a marker of intraventricular dyssynchrony. METHODS: The study aimed to analyze whether HPCSP corrects SF in patients with CRT indication, and if correction of SF predicts echocardiographic response. This retrospective analysis of prospectively collected data included 30 patients. Left ventricular ejection fraction (LVEF) was measured with echocardiography at baseline and at 6-month follow-up. Echocardiographic response was defined as increase in five points in LVEF. RESULTS: HPCSP shortened QRS duration by 48 ± 21 ms and SF was significantly decreased (baseline 3.6 ± 2.2 mm vs. HPCSP 1.5 ± 1.5 mm p < .0001). At 6-month follow-up, mean LVEF improvement was 8.6% ± 8.7% and 64% of patients were responders. There was a significant correlation between SF correction and increased LVEF (r = .61, p = .004). A correction of ≥1.5 mm (baseline SF - paced SF) had a sensitivity of 81% and 80% specificity to predict echocardiographic response (area under the curve 0.856, p = .019). CONCLUSION: HPCSP improves intraventricular dyssynchrony and results in 64% echocardiographic responders at 6-month follow-up. Dyssynchrony improvement with SF correction may predict echocardiographic response at 6-month follow-up.