Lipomatous Metaplasia Is Associated With Ventricular Tachycardia Recurrence Following Ablation in Patients With Nonischemic Cardiomyopathy.

BACKGROUND: Ventricular tachycardia (VT) recurrence rates remain high following ablation among patients with nonischemic cardiomyopathy (NICM). OBJECTIVES: This study sought to define the prevalence of lipomatous metaplasia (LM) in patients with NICM and VT and its association with postablation VT recurrence. METHODS: From patients who had ablation of left ventricular VT, we retrospectively identified 113 consecutive NICM patients with preprocedural contrast-enhanced cardiac computed tomography (CECT), from which LM was segmented. Nested within this cohort were 62 patients that prospectively underwent CECT and cardiac magnetic resonance from which myocardial border zone and dense late gadolinium enhancement (LGE) were segmented. A control arm of 30 NICM patients without VT with CECT was identified. RESULTS: LM was identified among 57% of control patients without VT vs 83% of patients without VT recurrence and 100% of patients with VT recurrence following ablation. In multivariable analyses, LM extent was the only independent predictor of VT recurrence, with an adjusted HR per 1-g LM increase of 1.1 (P < 0.001). Patients with LM extent ≥2.5 g had 4.9-fold higher hazard of VT recurrence than those with LM <2.5 g (P < 0.001). In the nested cohort with 32 VT recurrences, LM extent was independently associated with VT recurrence after adjustment for border zone and LGE extent (HR per 1 g increase: 1.1; P = 0.036). CONCLUSIONS: Myocardial LM is prevalent in patients with NICM of a variety of etiologies, and its extent is associated with postablation VT recurrence independent of the degree of fibrosis.

Programmed Ventricular Stimulation: Risk Stratification and Guiding Antiarrhythmic Therapies.

Electrophysiologic testing with programmed ventricular stimulation (PVS) has been utilized to induce ventricular tachycardia (VT), thereby improving risk stratification for patients with ischemic and nonischemic cardiomyopathies and determining the effectiveness of antiarrhythmic therapies, especially catheter ablation. A variety of procedural aspects can be modified during PVS in order to alter the sensitivity and specificity of the test including the addition of multiple baseline pacing cycle lengths, extrastimuli, and pacing locations. The definition of a positive result is also critically important, which has varied from exclusively sustained monomorphic VT (>30 seconds) to any ventricular arrhythmia regardless of morphology. In this review, we discuss the history of PVS and evaluate its role in sudden cardiac death risk stratification in a variety of patient populations. We propose an approach to future investigations that will capitalize on the unique ability to vary the sensitivity and specificity of this test. We then discuss the application of PVS during and following catheter ablation. The strategies that have been utilized to improve the efficacy of intraprocedural PVS are highlighted during a discussion of the limitations of this probabilistic strategy. The role of noninvasive programmed stimulation is also reviewed in predicting recurrent VT and informing management decisions including repeat ablations, modifications in antiarrhythmic drugs, and implantable cardioverter-defibrillator programming. Based on the available evidence and guidelines, we propose an approach to future investigations that will allow clinicians to optimize the use of PVS for risk stratification and assessment of therapeutic efficacy.

Class 1C Antiarrhythmics for Premature Ventricular Complex Suppression in Nonischemic Cardiomyopathy With Implantable Cardioverter-Defibrillators.

BACKGROUND: Premature ventricular complexes (PVCs) are common and associated with worse outcomes in patients with heart failure. Class 1C antiarrhythmic drugs (AADs) effectively suppress PVCs, but guidelines currently restrict their use in structural heart disease. OBJECTIVES: This study aimed to assess the safety and efficacy of class 1C AADs in patients with nonischemic cardiomyopathy (NICM) and implantable cardioverter-defibrillators (ICDs). METHODS: All patients with NICM and an ICD treated with flecainide or propafenone at the Hospital of the University of Pennsylvania between 2014 and 2022 were identified. PVC burden, left ventricular ejection fraction (LVEF), and biventricular pacing percentage were compared before and during class 1C AAD treatment. Safety outcomes included sustained atrial and ventricular arrhythmias, heart failure admissions, and death. RESULTS: We identified 34 patients, 23 receiving flecainide and 11 propafenone. Most patients (62%) had failed other AADs or catheter ablation (68%) prior to class 1C AAD initiation. PVC burden decreased from 20 ± 13% to 6 ± 7% (P < 0.001), LVEF increased from 33 ± 9% to 37 ± 10% (P = 0.01), and biventricular pacing percentage increased from 85 ± 9% to 93 ± 7% (P = 0.01). Sustained ventricular tachycardia (2 vs 9 patients) and admissions for decompensated heart failure (2 vs 3 patients) decreased compared with the 12 months prior to class 1C AAD initiation. CONCLUSIONS: Class 1C AADs effectively suppressed PVCs in patients with NICM and ICDs, leading to increases in LVEF and biventricular pacing percentage. In this limited sample, their use was safe. Larger studies are needed to confirm the safety of this approach.

Evaluation of organized atrial arrhythmias after cryptogenic stroke.

Background: Long-term rhythm monitoring to detect atrial fibrillation (AF) following a cryptogenic stroke (CS) is well established. However, the burden of organized atrial arrhythmias in this population is not well defined. Objective: The purpose of this study was to assess the incidence and risk factors for organized atrial arrhythmias in patients with CS. Methods: We evaluated all patients with CS who received an insertable cardiac monitor (ICM) between October 2014 and April 2020. All ICM transmissions categorized as AF, tachycardia, or bradycardia were reviewed. We evaluated the time to detection of organized AF and the combination of either organized atrial arrhythmia or AF. Results: A total of 195 CS patients with ICMs were included (51% men; mean age 66 ± 12 years; mean CHA2DS2-VASC score 4.6). Over mean follow-up of 18.9 ± 11.2 months, organized atrial arrhythmias lasting ≥30 seconds were detected in 45 patients (23%), of whom 62% did not have AF. Seventeen patients had both organized atrial arrhythmia and AF, and another 21 patients had AF only. Compared to those with normal left atrial size, patients with left atrial enlargement had a higher adjusted risk for development of atrial arrhythmias (mild left atrial enlargement: hazard ratio 1.99; 95% confidence interval 1.06-3.75; moderate/severe left atrial enlargement: hazard ratio 3.06; 95% confidence interval 1.58-5.92). Conclusion: Organized atrial arrhythmias lasting ≥30 seconds are detected in nearly one-fourth of CS patients. Two-thirds of these patients did not have AF. Further studies are required to evaluate the impact of organized atrial arrhythmias on recurrent stroke risk.

Predictors of nonpulmonary vein triggers for atrial fibrillation: A clinical risk score.

BACKGROUND: Targeting non-pulmonary vein triggers (NPVTs) after pulmonary vein isolation may reduce atrial fibrillation (AF) recurrence. Isoproterenol infusion and cardioversion of spontaneous or induced AF can provoke NPVTs but typically require vasopressor support and increased procedural time. OBJECTIVE: The purpose of this study was to identify risk factors for the presence of NPVTs and create a risk score to identify higher-risk subgroups. METHODS: Using the AF ablation registry at the Hospital of the University of Pennsylvania, we included consecutive patients who underwent AF ablation between January 2021 and December 2022. We excluded patients who did not receive NPVT provocation testing after failing to demonstrate spontaneous NPVTs. NPVTs were defined as non-pulmonary vein ectopic beats triggering AF or focal atrial tachycardia. We used risk factors associated with NPVTs with P <.1 in multivariable logistic regression model to create a risk score in a randomly split derivation set (80%) and tested its predictive accuracy in the validation set (20%). RESULTS: In 1530 AF ablations included, NPVTs were observed in 235 (15.4%). In the derivation set, female sex (odds ratio [OR] 1.40; 95% confidence interval [CI] 0.96-2.03; P = .080), sinus node dysfunction (OR 1.67; 95% CI 0.98-2.87; P = .060), previous AF ablation (OR 2.50; 95% CI 1.70-3.65; P <.001), and left atrial scar (OR 2.90; 95% CI 1.94-4.36; P <.001) were risk factors associated with NPVTs. The risk score created from these risk factors (PRE2SSS2 score; [PRE]vious ablation: 2 points, female [S]ex: 1 point, [S]inus node dysfunction: 1 point, left atrial [S]car: 2 points) had good predictive accuracy in the validation cohort (area under the receiver operating characteristic curve 0.728; 95% CI 0.648-0.807). CONCLUSION: A risk score incorporating predictors for NPVTs may allow provocation of triggers to be performed in patients with greatest expected yield.

Characteristics of the phenotype of mixed cardiomyopathy in patients with implantable cardioverter-defibrillators.

BACKGROUND OR PURPOSE: The prognosis of m ixed cardiomyopathy (CMP) in patients with implanted cardioverter-defibrillators (ICDs) has not been investigated. We aim to study the demographic, clinical, device therapies and survival characteristics of mixed CMP in a cohort of patients implanted with a defibrillator. METHODS: The term mixed CMP was used to categorise patients with impaired left ventricular ejection fraction attributed to documented non-ischemic triggers with concomitant moderate coronary artery disease. This is a single center observational cohort of 526 patients with a mean follow-up of 8.7 ± 3.5 years. RESULTS: There were 42.5% patients with ischemic cardiomyopathy (ICM), 26.9% with non-ischemic cardiomyopathy (NICM) and 30.6% with mixed CMP. Mixed CMP, compared to NICM, was associated with higher mean age (69.1 ± 9.6 years), atrial fibrillation (55.3%) and greater incidence of comorbidities. The proportion of patients with mixed CMP receiving device shocks was 23.6%, compared to 18.4% in NICM and 27% in ICM. The VT cycle length recorded in mixed CMP (281.6 ± 43.1 ms) was comparable with ICM (282.5 ± 44 ms; p = 0.9) and lesser than NICM (297.7 ± 48.7 ms; p = 0.1). All-cause mortality in mixed CMP (21.1%) was similar to ICM (20.1%; p = 0.8) and higher than NICM (15.6%; p = 0.2). The Kaplan-Meier curves revealed hazards of 1.57 (95% CI: 0.91, 2.68) for mixed CMP compared to NICM. CONCLUSION: In a cohort of patients with ICD, the group with mixed CMP represents a phenotype predominantly comprised of the elderly with a higher incidence of comorbidities. Mixed CMP resembles ICM in terms of number of device shocks and VT cycle length. Trends of long-term prognosis of patients with mixed CMP are worse than NICM and similar to ICM.

Accuracy of symptoms and pulse checking for detecting atrial fibrillation following catheter ablation.

BACKGROUND: There is growing interest in the possibility of discontinuing oral anticoagulation following successful catheter ablation of atrial fibrillation (AF). However, it remains unknown whether patients can accurately detect arrhythmia recurrences following ablation. We therefore sought to characterize the accuracy of pulse checking and arrhythmia symptoms for the identification of AF following ablation. METHODS: This prospective cohort study included patients at the Hospital of the University of Pennsylvania with an insertable cardiac monitor (ICM) treated with catheter ablation for AF who recorded the results from minimum twice daily pulse checks and additionally with arrhythmia symptoms into a diary for 2 months following their procedure. Accuracy of this self-assessment protocol was determined by comparison to ICM-detected AF. RESULTS: A total of 55 patients (age 69 ± 8 years, 30 (55%) male, CHA2DS2VASc score 3.2 ± 1. 5) were included. Patients recorded a total of 5911 pulse checks, and there were 280 episodes of ICM-documented AF among 26 patients with an average duration of 2.5 ± 3.3 h. Among 362 episodes of patient-suspected AF, 134 correlated with ICM-identified AF (37% true positive rate). Of the 5549 pulse checks that did not identify AF, 196 correlated with ICM-identified AF (4% false negative rate). Twice daily pulse checking had a sensitivity of 47% and a specificity of 96% for identifying each episode of AF. CONCLUSIONS: Our data indicate that a strategy of pulse checks and symptom assessment is insufficient to identify all episodes of AF in many patients following catheter ablation.

Substrate and arrhythmia characterization using the multi-electrode Optrell mapping catheter for ventricular arrhythmia ablation-a single-center experience.

BACKGROUND: The use of a multi-electrode Optrell mapping catheter during ventricular tachycardia (VT) or premature ventricular complex (PVC) ablation procedures has not been widely reported. OBJECTIVES: We aim to describe the feasibility and safety of using the Optrell multipolar mapping catheter (MPMC) to guide catheter ablation of VT and PVCs. METHODS: We conducted a single-center, retrospective evaluation of patients who underwent VT or PVC ablation between June and November 2022 utilizing the MPMC. RESULTS: A total of 20 patients met the inclusion criteria (13 VT and 7 PVC ablations, 80% male, 61 ± 15 years). High-density mapping was performed in the VT procedures with median 2753 points [IQR 1471-17,024] collected in the endocardium and 12,830 points [IQR 2319-30,010] in the epicardium. Operators noted challenges in manipulation of the MPMC in trabeculated endocardial regions or near valve apparatus. Late potentials (LPs) were detected in 11 cases, 7 of which had evidence of isochronal crowding demonstrated during late annotation mapping. Two patients who also underwent entrainment mapping had critical circuitry confirmed in regions of isochronal crowding. In the PVC group, high-density voltage and activation mapping was performed with a median 1058 points [IQR 534-3582] collected in the endocardium. CONCLUSIONS: This novel MPMC can be used safely and effectively to create high-density maps in LV endocardium or epicardium. Limitations of the catheter include a longer wait time for matrix formation prior to starting point collection and challenges in manipulation in certain regions.

One-year outcomes after stereotactic body radiotherapy for refractory ventricular tachycardia.

BACKGROUND: Cardiac stereotactic body radiotherapy (SBRT) has emerged as a promising noninvasive treatment for refractory ventricular tachycardia (VT). OBJECTIVE: The purpose of this study was to describe the safety and effectiveness of SBRT for VT in refractory to extensive ablation. METHODS: After maximal medical and ablation therapy, patients were enrolled in a prospective registry. Available electrophysiological and imaging data were integrated to generate a plan target volume. All SBRTs were planned with a single 25 Gy fraction using respiratory motion mitigation strategies. Clinical outcomes at 6 weeks, 6 months, and 12 months were analyzed and compared with the 6 months prior to treatment. VT burden (implantable cardioverter-defibrillator [ICD] shocks and antitachycardia pacing sequences) as well as clinical and safety outcomes were the main outcomes. RESULTS: Fifteen patients were enrolled and underwent planning. Fourteen (93%) underwent treatment, with 12 (80%) surviving to the end of the 6-week period and 10 (67%) surviving to 12 months. From 6 week to 12 months, there was recurrence of VT, which resulted in either appropriate antitachycardia pacing or ICD shocks in 33% (4 of 12). There were significant reductions in treated VT at 6 weeks to 6 months (98%) and at 12 months (99%) compared to the 6 months before treatment. There was a nonsignificant trend toward lower amiodarone dose at 12 months. Four deaths occurred after treatment, with no changes in ventricular function. CONCLUSION: For a select group of high-risk patients with VT refractory to standard therapy, SBRT is associated with a reduction in VT and appropriate ICD therapies over 1 year.

Detection of brain lesions after catheter ablation depends on imaging criteria: insights from AXAFA-AFNET 5 trial.

AIMS: Left atrial catheter ablation is well established in patients with symptomatic atrial fibrillation (AF) but associated with risk of embolism to the brain. The present analysis aims to assess the impact of diffusion-weighted imaging (DWI) slice thickness on the rate of magnetic resonance imaging (MRI)-detected ischaemic brain lesions after ablation. METHODS AND RESULTS: AXAFA-AFNET 5 trial (NCT02227550) participants underwent MRI using high-resolution (hr) DWI (slice thickness: 2.5-3 mm) and standard DWI (slice thickness: 5-6 mm) within 3-48 h after ablation. In 321 patients with analysable brain MRI (mean age 64 years, 33% female, median CHA2DS2-VASc 2), hrDWI detected at least one acute brain lesion in 84 (26.2%) patients and standard DWI in 60 (18.7%; P < 0.01) patients. High-resolution diffusion-weighted imaging detected more lesions compared to standard DWI (165 vs. 104; P < 0.01). The degree of agreement for lesion confirmation using hrDWI vs. standard DWI was substantial (κ = 0769). Comparing the proportion of DWI-detected lesions, lesion distribution, and total lesion volume per patient, there was no difference in the cohort of participants undergoing MRI at 1.5 T (n = 52) vs. 3 T (n = 269). CONCLUSION: The pre-specified AXAFA-AFNET 5 sub-analysis revealed significantly increased rates of MRI-detected acute brain lesions using hrDWI instead of standard DWI in AF patients undergoing ablation. In comparison to DWI slice thickness, MRI field strength had a no significant impact in the trial. Comparing the varying rates of ablation-related MRI-detected brain lesions across previous studies has to consider these technical parameters. Future studies should use hrDWI, as feasibility was demonstrated in the multicentre AXAFA-AFNET 5 trial.

Identifying Origin of Nonpulmonary Vein Triggers Using 2 Stationary Linear Decapolar Catheters: A Novel Algorithm.

BACKGROUND: Targeting nonpulmonary vein triggers (NPVTs) of atrial fibrillation (AF) after pulmonary vein isolation can be challenging. NPVTs are often single ectopic beats with a surface P-wave obscured by a QRS or T-wave. OBJECTIVES: The goal of this study was to construct an algorithm to regionalize the site of origin of NPVTs using only intracardiac bipolar electrograms from 2 linear decapolar catheters positioned in the posterolateral right atrium (along the crista terminalis with the distal bipole pair in the superior vena cava) and in the proximal coronary sinus (CS). METHODS: After pulmonary vein isolation in 42 patients with AF, pacing from 15 typical anatomic NPVT sites was conducted. For each pacing site, the electrogram activation sequence was analyzed from the CS catheter (simultaneous/chevron/inverse chevron/distal-proximal/proximal-distal) and activation time (ie, CSCTAT) between the earliest electrograms from the 2 decapolar catheters was measured referencing the earliest CS electrogram; a negative CSCTAT value indicates the crista terminalis catheter electrogram was earlier, and a positive CSCTAT value indicates the CS catheter electrogram was earlier. A regionalization algorithm with high predictive value was defined and tested in a validation cohort with AF NPVTs localized with electroanatomic mapping. RESULTS: In the study patient cohort (71% male; 43% with persistent AF, 52% with left atrial dilation), the algorithm grouped with high precision (positive predictive value 81%-99%, specificity 94%-100%, and sensitivity 30%-94%) the 15 distinct pacing sites into 9 clinically useful regions. Algorithm testing in a 98 patient validation cohort showed predictive accuracy of 91%. CONCLUSIONS: An algorithm defined by the activation sequence and timing of electrograms from 2 linear multipolar catheters provided accurate regionalization of AF NPVTs to guide focused detailed mapping.

Utility of Very High-Output Pacing to Identify VT Circuits in Patients Manifesting Traditionally Inexcitable Scar.

BACKGROUND: Entrainment and pace mapping are used to identify critical components (CCs) of ventricular tachycardia (VT) circuits. In patients with dense myocardial scarring, VT circuits may elude capture at standard high pacing outputs (up to 10 mA at a 2-millisecond pulse width). OBJECTIVES: The purpose of this study was to assess the utility of very high-output pacing (V-HOP, 50 mA at 2 milliseconds) for identifying CCs of VT circuits after standard high pacing output failed to elicit capture in densely scarred myocardial tissue. METHODS: Our standard VT ablation approach included electroanatomic mapping for substrate characterization and entrainment and/or pace mapping to identify CCs of VT circuits. Patients that required V-HOP to capture sites of interest comprised the study cohort. Ablation endpoints were VT termination and noninducibility. RESULTS: Twenty-five patients (71 ± 10 years of age, all males) undergoing 26 VT ablations met the inclusion criteria. The mean left ventricular ejection fraction was 30% ± 14%, and 85% had ischemic cardiomyopathy. V-HOP was used to successfully entrain VT in 17 patients, yielding central isthmus sites in 10 and entrance/exit sites in 4. VT terminated with radiofrequency ablation at these sites in 15 patients. In 9 patients, V-HOP identified scar locations with a delayed exit. Acute procedural success was achieved in 24 patients without any adverse events. Over a follow-up period of 16 ± 21 months, 2 patients experienced VT recurrence requiring repeat ablation during which the same location was targeted successfully in 1 patient. CONCLUSIONS: In VT patients with a dense scar that is traditionally inexcitable, V-HOP can identify CCs of the re-entrant circuit and guide successful ablation.

Septal Substrate Ablation Guided by Delayed Transmural Conduction Times: A Novel Ablation Approach to Target Intramural Substrates.

BACKGROUND: Intraprocedural identification of intramural septal substrate for ventricular tachycardia (ISS-VT) in nonischemic cardiomyopathy (NICM) is challenging. Delayed (>40 ms) transmural conduction time (DCT) with right ventricular basal septal pacing has been previously shown to identify ISS-VT. OBJECTIVES: This study sought to determine whether substrate catheter ablation incorporating areas of DCT may improve acute and long-term outcomes. METHODS: We included patients with NICM and ISS-VT referred for catheter ablation between 2016 and 2020. ISS-VT was defined by the following: 1) confluent septal areas of low unipolar voltage (<8.3 mV) in the presence of normal or minimal bipolar abnormalities; and 2) presence of abnormal electrograms in the septum. Substrate ablation was guided by the following: 1) activation and/or entrainment mapping for tolerated VT and pace mapping with ablation of abnormal septal electrograms for unmappable VTs (n = 57, Group 1); and 2) empirically extended to target areas of DCT during right ventricular basal septal pacing regardless of their participation in inducible VT(s) but sparing the conduction system when possible (n = 24, Group 2). RESULTS: There were no significant baseline differences between Groups 1 and 2. Noninducibility of any VT programmed stimulation at the end of ablation was higher in Group 2 compared with Group 1 (80% vs 53%; P = 0.03). At 12-month follow-up, single-procedure VT-free survival was significantly higher (79% vs 46%; P = 0.006) and the time to VT recurrence was longer (mean 10 ± 3 months vs 7 ± 4 months; P = 0.02) in Group 2 compared with Group 1. CONCLUSIONS: In patients with NICM and ISS-VT, a substrate ablation strategy that incorporates areas of DCT appears to improve freedom from recurrent VT.

Conduction Velocity Dispersion Predicts Postinfarct Ventricular Tachycardia Circuit Sites and Associates With Lipomatous Metaplasia.

BACKGROUND: Regional myocardial conduction velocity (CV) dispersion has not been studied in postinfarct patients with ventricular tachycardia (VT). OBJECTIVES: This study sought to compare the following: 1) the association of CV dispersion vs repolarization dispersion with VT circuit sites; and 2) myocardial lipomatous metaplasia (LM) vs fibrosis as the anatomic substrate for CV dispersion. METHODS: Among 33 postinfarct patients with VT, we characterized dense and border zone infarct tissue by late gadolinium enhancement cardiac magnetic resonance, and LM by computed tomography, with both images registered with electroanatomic maps. Activation recovery interval (ARI) was the time interval from the minimum derivative within the QRS complex to the maximum derivative within the T-wave on unipolar electrograms. CV at each EAM point was the mean CV between that point and 5 adjacent points along the activation wave front. CV and ARI dispersion were the coefficient of variation (CoV) of CV and ARI per American Heart Association (AHA) segment, respectively. RESULTS: Regional CV dispersion exhibited a much larger range than ARI dispersion, with median 0.65 vs 0.24; P < 0.001. CV dispersion was a more robust predictor of the number of critical VT sites per AHA segment than ARI dispersion. Regional LM area was more strongly associated with CV dispersion than fibrosis area. LM area was larger (median 0.44 vs 0.20 cm2; P < 0.001) in AHA segments with mean CV <36 cm/s and CoV_CV >0.65 than those with mean CV <36 cm/s and CoV_CV <0.65. CONCLUSIONS: Regional CV dispersion more strongly predicts VT circuit sites than repolarization dispersion, and LM is a critical substrate for CV dispersion.