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.

Correlation of Extent of Left Ventricular Endocardial Unipolar Low Voltage Zones with Ventricular Tachycardia in Non-ischemic Cardiomyopathy.

BACKGROUND: Endocardial electrogram (EGM) characteristics in non-ischemic cardiomyopathy (NICM) have not been explored adequately for prognostication. OBJECTIVES: We aim to study correlation of bipolar and unipolar EGM characteristics with left ventricular ejection fraction (LVEF) and ventricular tachycardia (VT) in NICM. METHODS: Electroanatomical mapping of LV was performed. Correlation of EGM characteristics with LVEF was performed. Differences between groups with and without VT and predictors of VT were studied. RESULTS: In 43 patients, unipolar EGM variables had better correlation with baseline LVEF than bipolar EGM variables: unipolar voltage (r=+0.36), peak negative unipolar voltage (r=-0.42), peak positive unipolar voltage (r=+0.38), and percentage area of unipolar LVZ (r=-0.41). Global mean unipolar voltage (HR- 0.4; 95% C.I 0.2-0.8), extent of unipolar LVZ (HR- 1.6; 95% CI 1.1-2.3) and % area of unipolar LVZ (HR- 1.6; 95% CI 1.1-2.3) were significant predictors of VT. For classification of patients with VT, extent of unipolar LVZ had AUC of 0.82 (95% CI 0.69-0.95; p<0.001), and % area of unipolar LVZ had AUC of 0.83 (95% CI 0.71-0.96; p=0.01). Cut-off of >3 segments for extent of unipolar LVZ had the best diagnostic accuracies (sensitivity- 90%; specificity- 67%) and cut-off of 33% for percentage area of unipolar LVZ had the best diagnostic accuracy (sensitivity- 95%; specificity- 60%) for VT. CONCLUSION: In NICM, extent and percentage area of unipolar low voltage zones are significant predictors of VT. Cut-offs of >3 segments of unipolar LVZ and >33% area of unipolar LVZ, have good diagnostic accuracies for association with VT.

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.

Risk of atrial arrhythmias in patients with ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: In arrhythmogenic right ventricular cardiomyopathy (ARVC), risk of atrial arrhythmias (AAs) persists after ventricular tachycardia (VT) ablation. OBJECTIVE: The purpose of this study was to determine the type, prevalence, outcome, and risk correlates of AA in ARVC in patients undergoing VT ablation. METHODS: Prospectively collected procedural and clinical data on ARVC patients undergoing VT ablation were analyzed. Risk score for typical atrial flutter was determined from univariate logistic regression analysis. RESULTS: Of 119 consecutive patients with ARVC and VT ablation, 40 (34%) had AA: atrial fibrillation (AF) in 31, typical isthmus-dependent atrial flutter (AFL) in 27, and atrial tachycardia/atypical flutter (AT) in 10. Seventeen patients (43%) with AA experienced inappropriate defibrillator therapy, with 15 patients experiencing shocks. Ablation was performed for typical AFL in 21 (53%), AT in 5 (13%), and pulmonary vein isolation for AF in 4 (10%) patients and prevented AA in 78% and all AFL during additional mean follow-up of 65 months. Risk score for typical flutter included age >40 years (1 point), ≥moderate right ventricular dysfunction (2 points), ≥moderate tricuspid regurgitation (2 points), ≥moderate right atrial dilation (2 points), and right ventricular volume >250 cc (3points), with score >4 identifying 50% prevalence of typical flutter. CONCLUSION: AAs are common in patients with ARVC and VT, can result in inappropriate implantable cardioverter-defibrillator shocks, and typically are controlled with atrial ablation. A risk score can be used to identify patients at high risk for typical AFL who may be considered for isthmus ablation at the time of VT ablation.

Intraoperative ultrasound-guided pectoral nerve blocks for cardiac implantable device procedures.

BACKGROUND: Pectoral nerve (PECs) blocks are established regional anesthesia techniques that can provide analgesia to the anterior chest wall. Although commonly performed preoperatively by anesthesiologists, the feasibility of electrophysiologist-performed PECs blocks from within cardiac implantable electronic device (CIED) pockets at the time of implantation has not been established. The objective of this study is to assess the feasibility of routine PECs blocks performed by the electrophysiologist from within the exposed device pocket at the time of CIED procedures. METHODS: Patients undergoing CIED procedures underwent a PECs I block (15 cc of 1% lidocaine/0.25% bupivacaine) injected between the pectoralis major and minor muscles guided by ultrasound placed in the device pocket, or PECs II block, which included a second injection (15 cc) between pectoralis minor and serratus anterior muscles. Postoperatively, pain was assessed on a numeric scale (0-10) at 1, 2, 4, and 24 h, and 2 weeks after the procedure. RESULTS: Among 20 patients (age 65 ± 16 years, 70% male, 55% with history of chronic pain), PECs I (75%) and PECs II (25%) blocks were performed. The procedures were de novo implantation (n = 17) or device revision (n = 3). The average pain score in the first 4 h was 0.4 ± 0.8 and 0.3 ± 0.6 at 24 h after the procedure. During the 24-h postoperative period, 4 patients received opioids. Two patients were discharged with opioids for pain unrelated to the procedure. CONCLUSIONS: Intraoperative PECs blocks can be feasibly performed from within an exposed pocket at the time of CIED procedures with minimal postoperative pain.

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.

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.

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.

Impact of Median Sternotomy on Safety and Efficacy of the Subcutaneous Implantable Cardioverter Defibrillator.

BACKGROUND: Subcutaneous implantable cardioverter defibrillators (S-ICDs) are an attractive alternative to transvenous ICDs among those not requiring pacing. However, the risks of damage to the S-ICD electrode during sternotomy and adverse interactions with sternal wires remain unclear. We sought to determine the rates of damage to the S-ICD lead during sternotomy, inappropriate shocks from electrical noise due to interaction with sternal wires, and failure to terminate spontaneous or induced ventricular arrhythmias. METHODS: Retrospective, multicenter study of patients undergoing sternotomy before or after S-ICD implantation. Clinical, procedural, and device-related data were collected by each center and analyzed by the coordinating center. These data were compared with a historical control cohort of nonsternotomy patients. RESULTS: Of 196 identified patients (52±16 years, 47 women), 166 underwent S-ICD implantation after sternotomy and 30 sternotomy after S-ICD. There was no damage to any lead among those who underwent sternotomy after S-ICD. Defibrillation threshold testing was performed in 63% at implant, with 91% first shock success. During a median follow-up of 29 months (range, 1-188), S-ICD first shocks successfully terminated spontaneous ventricular arrhythmias in 31 of 32 patients (97%). Inappropriate shocks occurred in 22 patients, most commonly related to T wave oversensing (n=14). Compared with the nonsternotomy controls, there were no differences in rates of first shock success for induced or spontaneous arrhythmias or rate of inappropriate shocks. CONCLUSIONS: Sternotomy before or after S-ICD does not confer additional risk relative to a historical control group without sternotomy.