Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy.

BACKGROUND: Desmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce. OBJECTIVES: This study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multicenter cohort. METHODS: We collected phenotypic and outcomes data from 16 families with DES-related ACM from 10 European centers. We assessed in vitro DES aggregates. Major cardiac events were compared to historical controls with lamin A/C truncating variant (LMNA-tv) and filament C truncating variant (FLNC-tv) ACM. RESULTS: Of 82 patients (54% males, median age: 36 years), 11 experienced sudden cardiac death (SCD) (n = 7) or heart failure death (HFd)/heart transplantation (HTx) (n = 4) before clinical evaluation. Among 68 survivors, 59 (86%) presented signs of cardiomyopathy, with left ventricular (LV) dominant (50%) or biventricular (34%) disease. Mean LV ejection fraction was 51% ± 13%; 36 of 53 had late gadolinium enhancement (ring-like pattern in 49%). During a median of 6.73 years (Q1-Q3: 3.55-9.52 years), the composite endpoint (sustained ventricular tachycardia, aborted SCD, implantable cardioverter-defibrillator therapy, SCD, HFd, and HTx) was achieved in 15 additional patients with HFd/HTx (n = 5) and SCD/aborted SCD/implantable cardioverter-defibrillator therapy/sustained ventricular tachycardia (n = 10). Male sex (P = 0.004), nonsustained ventricular tachycardia (P = 0.017) and LV ejection fraction ≤50% (P = 0.012) were associated with the composite endpoint. Males with DES variants had similar outcomes to historical FLNC-tv and LMNA-tv controls. However, females showed better outcomes than those with LMNA-tv. In vitro experiments showed the characteristic finding of DES aggregates in 7 of 12 variants. CONCLUSIONS: DES ACM is associated with poor outcomes which can be predicted with potentially successful treatments, underscoring the importance of familial evaluation and genetic studies to identify at risk individuals.

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.

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.

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.

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.

Premature ventricular complex site of origin and ablation outcomes in patients with diabetes mellitus.

BACKGROUND: Premature ventricular complexes (PVCs) are frequent in patients with diabetes mellitus (DM). Still, the PVCs characteristics as well as the outcomes after catheter ablation in this population remain unknown. Aim of the study was to describe principal features of PVCs ablated in a wide DM-patients cohort and report postablation clinical outcomes in the follow-up of patients with DM and left ventricular dysfunction. METHODS: From April 2012 to April 2020 data of 544 patients (315 [58%] men, 55±16 y), consecutive patients submitted for PVC ablation, were prospectively collected. Patients with left ventricle (LV) systolic disfunction (LVEF<50%) were included in a prospective protocol and followed at 6 and 12 months, and annually thereafter. Baseline characteristic as well ablation outcomes were analyzed based on the presence of DM. RESULTS: Sixty (11%) patients had DM. Patients with DM more frequently had a PVC's site of origin (SOO) in the LV (45 [75%] vs. 229 [48%], P<0.001). The most frequent PVC's SOO in DM patients was the LV outflow tract (OT) (35 [58%] patients: 12 aortic cusps; 12 LV summit; 11 in the myocardium immediately inferior to the valvular plane). Fifty-five (92%) patients with DM had an acute successful ablation, without differences compared with patients without DM (55 [92%] vs. 437 [90%], P=0.9). Twenty-tree (38%) DM-patients had LV dysfunction at the ablation time. In these patients, mean PVC burden decreased from 26±11% at baseline to 4±5% (P<0.001); LVEF increased from 36±8% to 42±11% (P<0.01) and NYHA class improved from 2.2±0.6 to 1.8+0.5 (P<0.01), after a mean follow-up of 37±14 months. CONCLUSIONS: Patients with DM frequently have PVC with a LV-SOO, being the LVOT the most frequent SOO in this population. Among DM patients with LV dysfunction, ablation persistently and significantly reduce the PVC burden improving functional status. Patients with DM have lower benefit in terms of LV function recovery after ablation compared with non-diabetic patients.

Validation of multiparametric approaches for the prediction of sudden cardiac death in patients with Brugada syndrome and electrophysiological study.

INTRODUCTION AND OBJECTIVES: Multiparametric scores have been designed for better risk stratification in Brugada syndrome (BrS). We aimed to validate 3 multiparametric approaches (the Delise score, Sieira score and the Shanghai BrS Score) in a cohort with Brugada syndrome and electrophysiological study (EPS). METHODS: We included patients diagnosed with BrS and previous EPS between 1998 and 2019 in 23 hospitals. C-statistic analysis and Cox proportional hazard regression models were used. RESULTS: A total of 831 patients were included (mean age, 42.8±13.1; 623 [75%] men; 386 [46.5%] had a type 1 electrocardiogram (ECG) pattern, 677 [81.5%] were asymptomatic, and 319 [38.4%] had an implantable cardioverter-defibrillator). During a follow-up of 10.2±4.7 years, 47 (5.7%) experienced a cardiovascular event. In the global cohort, a type 1 ECG and syncope were predictive of arrhythmic events. All risk scores were significantly associated with events. The discriminatory abilities of the 3 scores were modest (particularly when these scores were evaluated in asymptomatic patients). Evaluation of the Delise and Sieira scores with different numbers of extra stimuli (1 or 2 vs 3) did not substantially improve the event prediction c-index. CONCLUSIONS: In BrS, classic risk factors such as ECG pattern and previous syncope predict arrhythmic events. The predictive capabilities of the EPS are affected by the number of extra stimuli required to induce ventricular arrhythmias. Scores combining clinical risk factors with EPS help to identify the populations at highest risk, although their predictive abilities remain modest in the general BrS population and in asymptomatic patients.

Cardiovascular magnetic resonance determinants of ventricular arrhythmic events after myocardial infarction.

AIMS: To non-invasively characterize, by means of late gadolinium enhancement cardiac magnetic resonance (LGE-CMR), scar differences, and potential variables associated with ventricular tachycardia (VT) occurrence in chronic post-myocardial infarction (MI) patients. METHODS AND RESULTS: A case-control study was designed through retrospective LGE-CMR data analysis of chronic post-MI patients (i) consecutively referred for VT substrate ablation after a first VT episode (n = 66) and (ii) from a control group (n = 84) with no arrhythmia evidence. The myocardium was characterized differentiating core, border zone (BZ), and BZ channels (BZCs) using the ADAS 3D post-processing imaging platform. Clinical and scar characteristics, including a novel parameter, the BZC mass, were compared between both groups. One hundred and fifty post-MI patients were included. Four multivariable Cox proportional hazards regression models were created for total scar mass, BZ mass, core mass, and BZC mass, adjusting them by age, sex, and left ventricular ejection fraction (LVEF). A cut-off of 5.15 g of BZC mass identified the cases with 92.4% sensitivity and 86.9% specificity [area under the ROC curve (AUC) 0.93 (0.89-0.97); P < 0.001], with a significant increase in the AUC compared to other scar parameters (P < 0.001 for all pairwise comparisons). Adding BZC mass to LVEF allowed to reclassify 33.3% of the cases and 39.3% of the controls [net reclassification improvement = 0.73 (0.71-0.74)]. CONCLUSIONS: The mass of BZC is the strongest independent variable associated with the occurrence of sustained monomorphic ventricular tachycardia in post-MI patients after adjustment for age, sex, and LVEF. Border zone channel mass measurement could permit a more accurate VT risk stratification than LVEF in chronic post-MI patients.

Impact of a predefined pacemapping protocol use for ablation of infrequent premature ventricular complexes: A prospective, multicenter study.

BACKGROUND: Pacemapping (PM) is a useful maneuver for aiding premature ventricular complex (PVC) ablation. Its standalone clinical value is still to be defined. OBJECTIVES: The purpose of this study was to analyze the efficacy of a predefined PM protocol for low-burden PVC ablation, regardless of their site of origin (SOO) and the presence of structural heart disease. METHODS: This was a prospective, nonrandomized, multicenter study. The PM protocol was performed when <1 PVC/min was found. The "target area" was delimited by the 3 best matching points >94% correlation, and 3 radiofreqency (RF) applications were delivered. RESULTS: Of 185 patients, 105 (57%) underwent activation mapping, 60 (32%) were PM-guided, and 20 (11%) were canceled due to absence of PVCs. Baseline QRS, PVC burden, and outflow tract origin were independent predictors of PM-guided ablation. A higher proportion of right ventricular outflow tract SOO in the PM group (52% vs 40%; P = .03) was observed. Mean target area was 0.6 ± 0.9 cm2. Mean 10-ms isochronal area in local activation time (LAT)-guided procedures was higher (1.7 ± 2.3 cm2; P <.001). Mean number of PM matching points acquired was 39 ± 21 (range 6-98). Mean mapping and RF times were similar in both groups. However, significantly shorter procedural (53 ± 24 vs 61 ± 26 minutes; P = .04) as well as RF times (111 ± 51 vs 149 ± 149 seconds; P = .05) were needed in the PM group using the proposed protocol. Global clinical success reached 87% for the PM group and 90% (P = .58) the for LAT mapping group. CONCLUSION: When LAT mapping is precluded, application of a PM-guided ablation protocol directed to >94% matching correlation target area is a more efficient alternative with comparable clinical results.

MANual vs. automatIC local activation time annotation for guiding Premature Ventricular Complex ablation procedures (MANIaC-PVC study).

AIMS: To assess potential benefits of a local activation time (LAT) automatic acquisition protocol using wavefront annotation plus an ECG pattern matching algorithm [automatic (AUT)-arm] during premature ventricular complex (PVC) ablation procedures. METHODS AND RESULTS: Prospective, randomized, controlled, and international multicentre study (NCT03340922). One hundred consecutive patients with indication for PVC ablation were enrolled and randomized to AUT (n = 50) or manual (MAN, n = 50) annotation protocols using the CARTO3 navigation system. The primary endpoint was mapping success. Clinical success was defined as a PVC-burden reduction of ≥80% in the 24-h Holter within 6 months after the procedure. Mean age was 56 ± 14 years, 54% men. The mean baseline PVC burden was 25 ± 13%, and mean left ventricular ejection fraction (LVEF) 55 ± 11%. Baseline characteristics were similar between the groups. The most frequent PVC-site of origin were right ventricular outflow tract (41%), LV (25%), and left ventricular outflow tract (17%), without differences between groups. Radiofrequency (RF) time and number of RF applications were similar for both groups. Mapping and procedure times were significantly shorter in the AUT-arm (25.5 ± 14.3 vs. 32.8 ± 12.6 min, P = 0.009; and 54.8 ± 24.8 vs. 67.4 ± 25.2, P = 0.014, respectively), while more mapping points were acquired [136 (94-222) AUT vs. 79 (52-111) MAN; P < 0.001]. Mapping and clinical success were similar in both groups. There were no procedure-related complications. CONCLUSION: The use of a complete automatic protocol for LAT annotation during PVC ablation procedures allows to achieve similar clinical endpoints with higher procedural efficiency when compared with conventional, manual annotation carried out by expert operators.

Long-term prognosis of women with Brugada syndrome and electrophysiological study.

BACKGROUND: A male predominance in Brugada syndrome (BrS) has been widely reported, but scarce information on female patients with BrS is available. OBJECTIVE: The purpose of this study was to investigate the clinical characteristics and long-term prognosis of women with BrS. METHODS: A multicenter retrospective study of patients diagnosed with BrS and previous electrophysiological study (EPS) was performed. RESULTS: Among 770 patients, 177 (23%) were female. At presentation, 150 (84.7%) were asymptomatic. Females presented less frequently with a type 1 electrocardiographic pattern (30.5% vs 55.0%; P <.001), had a higher rate of family history of sudden cardiac death (49.7% vs 29.8%; P <.001), and had less sustained ventricular arrhythmias (VAs) on EPS (8.5% vs 15.1%; P = .009). Genetic testing was performed in 79 females (45% of the sample) and was positive in 34 (19%). An implantable cardioverter-defibrillator was inserted in 48 females (27.1%). During mean (± SD) follow-up of 122.17 ± 57.28 months, 5 females (2.8%) experienced a cardiovascular event compared to 42 males (7.1%; P = .04). On multivariable analysis, a positive genetic test (18.71; 95% confidence interval [CI] 1.82-192.53; P = .01) and atrial fibrillation (odds ratio 21.12; 95% CI 1.27-350.85; P = .03) were predictive of arrhythmic events, whereas VAs on EPS (neither with 1 or 2 extrastimuli nor 3 extrastimuli) were not. CONCLUSION: Women with BrS represent a minor fraction among patients with BrS, and although their rate of events is low, they do not constitute a risk-free group. Neither clinical risk factors nor EPS predicts future arrhythmic events. Only atrial fibrillation and positive genetic test were identified as risk factors for future arrhythmic events.

Arrhythmogenic substrate detection in chronic ischaemic patients undergoing ventricular tachycardia ablation using multidetector cardiac computed tomography: compared evaluation with cardiac magnetic resonance.

AIMS: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) permits characterizing ischaemic scars, detecting heterogeneous tissue channels (HTCs) which constitute the arrhythmogenic substrate (AS). Late gadolinium enhancement cardiac magnetic resonance also improves the arrhythmia-free survival when used to guide ventricular tachycardia (VT) substrate ablation. However, its availability may be limited. We sought to evaluate the performance of multidetector cardiac computed tomography (MDCT) imaging in identifying HTCs detected by LGE-CMR in ischaemic patients undergoing VT substrate ablation. METHODS AND RESULTS: Thirty ischaemic patients undergoing both LGE-CMR and MDCT before VT substrate ablation were included. Using a dedicated post-processing software, two blinded operators, assigned either to LGE-CMR or MDCT analysis, characterized the presence of CMR and computed tomography (CT) channels, respectively. Cardiac magnetic resonance channels were classified as endocardial (layers < 50%), epicardial (layers ≥ 50%), or transmural. Cardiac magnetic resonance- vs. CT-channel concordance was considered when showing the same orientation and American Heart Association (AHA) segment. Mean age was 69 ± 10 years; 90% were male. Mean left ventricular ejection fraction was 35 ± 10%. All patients had CMR channels (n = 76), whereas only 26/30 (86.7%) had CT channels (n = 91). Global sensitivity (Se) and positive predictive values for detecting CMR channels were 61.8% and 51.6%, respectively. MDCT performance improved in patients with epicardial CMR channels (Se 80.5%) and transmural scars (Se 72.2%). In 4/11 (36%) patients with subendocardial myocardial infarction (MI), MDCT was unable to identify the AS. CONCLUSIONS: Compared to LGE-CMR, myocardial wall thickness assessment using MDCT fails to detect the presence of AS in 36% of patients with subendocardial MI, showing modest sensitivity identifying HTCs but a better performance in patients with transmural scars.

Premature ventricular complex site of origin and ablation outcomes in patients with prior myocardial infarction.

BACKGROUND: Frequent premature ventricular complexes (PVCs) are common after a myocardial infarction (MI), but data on PVC ablation in this population are limited. OBJECTIVE: The purpose of this study was to analyze data on PVC ablation in post-MI patients. METHODS: Three hundred thirty-two patients with frequent PVCs and left ventricular (LV) dysfunction were prospectively studied. Data from 67 patients (20%; age 63 ± 10 years; 65 men [93%]) with previous MI were compared with the remaining 265 patients. RESULTS: PVCs in post-MI patients originate predominantly from the LV (92% LV vs 6% right ventricle [RV]; P <.001). The most frequent sites of origin (SOO) were MI scar in 23 patients (34%) and left ventricular outflow tract (LVOT) in 22 patients (33%). A papillary muscle origin was more frequent in post-MI patients (16% vs 4%; P = .001), whereas an RV outflow tract origin was less frequent (1% vs 33%; P <.001) compared to patients without MI. In post-MI patients, PVC burden decreased from 29% ± 12% at baseline to 4.6% ± 7% (P <.001); left ventricular ejection fraction (LVEF) improved from 33.6% ± 8% to 42% ± 10% (P <.001); and New York Heart Association functional class improved from 2.1 ± 0.7 to 1.4 ± 0.5 points (P <.001) at 12 months. Compared with the remaining 265 patients, there were no differences in acute ablation success (85% vs 85%; P = .45), complication rate (6% vs 6%; P = .41), or absolute improvement in LVEF (8.8 ± 10 vs 9.9 ± 11 absolute points; P = .38). CONCLUSION: PVC ablation significantly improves cardiac function and functional status in post-MI patients. PVCs predominantly originate from MI scar and LVOT. A papillary muscle SOO was found to be strongly associated with previous MI.

Safety and Outcomes of Ventricular Tachycardia Substrate Ablation During Sinus Rhythm: A Prospective Multicenter Registry.

OBJECTIVES: This study sought to analyze safety and outcomes of ventricular tachycardia (VT) substrate ablation during sinus rhythm (SR), without baseline VT induction. BACKGROUND: Safety and outcomes after scar-related VT ablation during SR are not well known. Hemodynamic instability and need for electrical cardioversion can compromise safety of VT ablation procedures. METHODS: Four hundred twelve consecutive patients with structural heart disease undergoing VT ablation were included in a prospective multicenter registry. Substrate ablation during SR, without baseline VT induction, was the first step of the ablation procedure and the standard protocol. Scar dechanneling was the substrate ablation technique used. VT inducibility was tested after substrate ablation. RESULTS: VT induction protocol was negative after substrate ablation in 289 patients (70.1%), completing the procedure in SR. Procedure-related complication rate was 6.5%, including 1 death (0.2%). Thirty-day mortality after first VT ablation procedure was 1.7%. Overall survival was 95.8% and 88.6% at 1 and 3 years of follow-up, respectively. In a multivariable proportional hazards regression model, age ≥70 years (hazard ratio [HR]: 4.95 [2.59 to 9.47]; p < 0.001), chronic obstructive pulmonary disease (HR: 2.37 [1.24 to 4.52]; p = 0.008), left ventricular ejection fraction <30% (HR: 2.43 [1.37 to 4.33]; p = 0.002), and incomplete substrate ablation (HR: 2.37 [1.24 to 4.52]; p = 0.026) were independent predictors of overall mortality. At 12 months' follow-up, VT-free survival was 82.5% after 1 procedure and 87.8% after n procedures CONCLUSIONS: Substrate ablation during SR avoiding multiple VT induction has low procedure-related complications and low early mortality. Age, chronic obstructive pulmonary disease, and reduced left ventricular ejection fraction, but also incomplete substrate elimination, are predictors of mortality.

Ventricular arrhythmia risk is associated with myocardial scar but not with response to cardiac resynchronization therapy.

AIMS: Sudden cardiac death (SCD) risk estimation in patients referred for cardiac resynchronization therapy (CRT) remains a challenge. By CRT-mediated improvement of left ventricular ejection fraction (LVEF), many patients loose indication for primary prevention implantable cardioverter-defibrillator (ICD). Increasing evidence shows the importance of myocardial scar for risk prediction. The aim of this study was to investigate the prognostic impact of myocardial scar depending on the echocardiographic response in patients undergoing CRT. METHODS AND RESULTS: Patients with indication for CRT were prospectively enrolled. Decision about ICD or pacemaker implantation was based on clinical criteria. All patients underwent delayed-enhancement cardiac magnetic resonance imaging. Median follow-up duration was 45 (24-75) months. Primary outcome was a composite of sustained ventricular arrhythmia, appropriate ICD therapy, or SCD. A total of 218 patients with LVEF 25.5 ± 6.6% were analysed [158 (73%) male, 64.9 ± 10.7 years]. Myocardial scar was observed in 73 patients with ischaemic cardiomyopathy (ICM) (95% of ICM patients); in 62 with non-ischaemic cardiomyopathy (45% of these patients); and in all but 1 of 36 (17%) patients who reached the primary outcome. Myocardial scar was the only significant predictor of primary outcome [odds ratio 27.7 (3.8-202.7)], independent of echocardiographic CRT response. A total of 55 (25%) patients died from any cause or received heart transplant. For overall survival, only a combination of the absence of myocardial scar with CRT response was associated with favourable outcome. CONCLUSION: Malignant arrhythmic events and SCD depend on the presence of myocardial scar but not on CRT response. All-cause mortality improved only with the combined absence of myocardial scar and CRT response.

Automatic Detection of Slow Conducting Channels during Substrate Ablation of Scar-Related Ventricular Arrhythmias.

BACKGROUND: Voltage mapping allows identifying the arrhythmogenic substrate during scar-related ventricular arrhythmia (VA) ablation procedures. Slow conducting channels (SCCs), defined by the presence of electrogram (EGM) signals with delayed components (EGM-DC), are responsible for sustaining VAs and constitute potential ablation targets. However, voltage mapping, as it is currently performed, is time-consuming, requiring a manual analysis of all EGMs to detect SCCs, and its accuracy is limited by electric far-field. We sought to evaluate an algorithm that automatically identifies EGM-DC, classifies mapping points, and creates new voltage maps, named "Slow Conducting Channel Maps" (SCC-Maps). METHODS: Retrospective analysis of electroanatomic maps (EAM) from 20 patients (10 ischemic, 10 with arrhythmogenic right ventricular dysplasia/cardiomyopathy) was performed. EAM voltage maps were acquired during sinus rhythm and used for ablation. Preprocedural contrast-enhanced cardiac magnetic resonance (Ce-CMR) imaging was available for the ischemic population. Three mapping modalities were analysed: (i) EAM voltage maps using standard (EAM standard) or manual (EAM screening) thresholds for defining core and border zones; (ii) SCC-Maps derived from the use of the novel SCC-Mapping algorithm that automatically identify EGM-DCs measuring the voltage of the local component; and (iii) Ce-CMR maps (when available). The ability of each mapping modality in identifying SCCs and their agreement was evaluated. RESULTS: SCC-Maps and EAM screening identified a greater number of SCC entrances than EAM standard (3.45 ± 1.61 and 2.95 ± 2.31, resp., vs. 1.05 ± 1.10; p < 0.01). SCC-Maps and EAM screening highly correlate with Ce-CMR maps in the ischemic population when compared to EAM standard (Lin's correlation = 0.628 and 0.679, resp., vs. 0.212, p < 0.01). CONCLUSION: The SCC-Mapping algorithm allows an operator-independent analysis of EGM signals showing better identification of the arrhythmogenic substrate characteristics when compared to standard voltage EAM.

Cardiac Magnetic Resonance-Guided Ventricular Tachycardia Substrate Ablation.

OBJECTIVES: This study assessed the feasibility and potential benefit of performing ventricular tachycardia (VT) substrate ablation procedures guided by cardiac magnetic resonance (CMR)-derived pixel signal intensity (PSI) maps. BACKGROUND: CMR-aided VT ablation using PSI maps from late gadolinium enhancement-CMR (LGE-CMR), together with electroanatomical map (EAM) information, has been shown to improve outcomes of VT substrate ablation. METHODS: Eighty-four patients with scar-dependent monomorphic VT who underwent substrate ablation were included in the study. In the last 28 (33%) consecutive patients, the procedure was guided by CMR. Procedural data, as well as acute and follow-up outcomes, were compared between patients who underwent guided CMR and 2 control groups: 1) patients who had PSI maps were available but the EAM was acquired and used to select the ablation targets (CMR aided); and 2) patients with no CMR-derived PSI maps available (no CMR). RESULTS: Mean procedure duration was lower in CMR-guided substrate ablation compared with CMR-aided and no CMR (107 ± 59 min vs. 203 ± 68 min and 227 ± 52 min; p < 0.001 for both comparisons). CMR-guided ablation required less fluoroscopy time than CMR-aided ablation and no CMR (10 ± 4 min vs. 23 ± 11 min and 20 ± 9 min, respectively; p < 0.001 for both comparisons) and less radiofrequency time (15 ± 8 min vs. 20 ± 15 min and 26 ± 10 min; p = 0.16 and p < 0.001, respectively). After substrate ablation, VT inducibility was lower in CMR-guided ablation compared with CMR-aided ablation and no CMR (18% vs. 32% and 46%; p = 0.35 and p = 0.04, respectively), without significant differences in complications. After 12 months, VT recurrence was lower in those who underwent CMR-guided ablation compared with no CMR (log-rank: 0.019), with no differences with CMR-aided ablation. CONCLUSIONS: CMR-guided VT ablation is feasible and safe, significantly reduces the procedural, fluoroscopy, and radiofrequency times, and is associated with a higher noninducibility rate and lower VT recurrence after substrate ablation.

Follow-Up After Myocardial Infarction to Explore the Stability of Arrhythmogenic Substrate: The Footprint Study.

OBJECTIVES: This study aimed to characterize the long-term scar remodeling process after an acute myocardial infarction (AMI) and the underlying scar-related arrhythmogenic substrate using serial late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). BACKGROUND: Little is known about the time course needed for completion of the scar healing process after an AMI, which can be assessed by noninvasive cardiac imaging techniques such as LGE-CMR. METHODS: Fifty-six patients with revascularized ST-segment elevation AMI (STEMI) were consecutively included. LGE-CMR (3-T) was obtained at 7 days, 6 months, and 4 years after STEMI. The myocardium was segmented into 10 layers from the endocardium to epicardium, characterizing the core, border zone (BZ), and BZ channels (BZCs) using a dedicated post-processing software. RESULTS: Mean age of the patients was 57 ± 11 years; 77% were men. Left ventricular ejection fraction improved at 6 months from 47% to 51% (p < 0.001) and remained stable at 4 years (53%; p = 0.21). Total scar mass decreased from 20.3 ± 14.6 g to 15.3 ± 13.3 g (6 months) and to 12.7 ± 11.7 g (4 years) (p < 0.001). Thirty of 56 (53%) patients showed a mean of 1.5 ± 1.3 BZCs/patient at 7 days, decreasing to 1.2 ± 1.3 (6 months) and 0.8 ± 1.0 (4 years) (p < 0.01). Only 42% of the initial BZCs remained present after 4 years. There were no arrhythmic events after a mean follow-up of 62.5 ± 7.4 months. CONCLUSIONS: CMR data post-processing permitted a dynamic assessment of quantitative and qualitative post-AMI scar characteristics. Scar size and number of BZCs steadily decreased 4 years after AMI. BZC distribution was significantly modified during this time. These dynamic parameters could be reliably assessed with CMR; their evaluation might be of prognostic value.

Influence of baseline QRS on the left ventricular ejection fraction recovery after frequent premature ventricular complex ablation.

AIMS: Frequent premature ventricular complexes (PVCs) can induce or worsen left ventricular systolic dysfunction. We aimed to investigate the influence of the baseline QRS in the response after PVC ablation in patients with depressed left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Two hundred and fifteen [59 ± 13 years old, 152 (71%) men] consecutive patients with left ventricular (LV) systolic dysfunction and frequent PVCs referred for ablation were included and followed-up for 12 months. Echocardiographic response was defined as an improvement of at least five absolute points in LVEF. Clinical, electrocardiogram, and electrophysiological characteristics were analysed. Mean baseline QRS duration was 110 ms [97-140]. Premature ventricular complex burden significantly decreased after ablation from 23% [16-33] at baseline to 1% [0-8] at 12 months, P < 0.001. Mean PVC burden reduction was 18 [8-30] points. There was a significant improvement of LVEF from 35% [29-40] at baseline to 44% [35-55] at 12 months, P < 0.001. One hundred and thirty (61%) patients were considered as echocardiographic responders. Baseline QRS duration (ms) [odds ratio (OR) 0.98 (0.97-0.99), P = 0.01] was an independent predictor of echocardiographic response. Mean LVEF improvement was 16 [10-21] points when the baseline QRS duration was <90 ms; 12 [4-20] when it was 90-110 ms; 5 [0-15] when it was 110 ± 130 ms; and 0 [0-6] points when it was >130 ms. CONCLUSIONS: In patients with LV systolic dysfunction, intrinsic QRS duration is inversely related to the probability and the degree of echocardiographic response after frequent PVC ablation. Patients with a QRS duration >130 ms at baseline have the poorer response after ablation.