Advances in Cardiac Electrophysiology.

Despite the global COVID-19 pandemic, during the past 2 years, there have been numerous advances in our understanding of arrhythmia mechanisms and diagnosis and in new therapies. We increased our understanding of risk factors and mechanisms of atrial arrhythmias, the prediction of atrial arrhythmias, response to treatment, and outcomes using machine learning and artificial intelligence. There have been new technologies and techniques for atrial fibrillation ablation, including pulsed field ablation. There have been new randomized trials in atrial fibrillation ablation, giving insight about rhythm control, and long-term outcomes. There have been advances in our understanding of treatment of inherited disorders such as catecholaminergic polymorphic ventricular tachycardia. We have gained new insights into the recurrence of ventricular arrhythmias in the setting of various conditions such as myocarditis and inherited cardiomyopathic disorders. Novel computational approaches may help predict occurrence of ventricular arrhythmias and localize arrhythmias to guide ablation. There are further advances in our understanding of noninvasive radiotherapy. We have increased our understanding of the role of His bundle pacing and left bundle branch area pacing to maintain synchronous ventricular activation. There have also been significant advances in the defibrillators, cardiac resynchronization therapy, remote monitoring, and infection prevention. There have been advances in our understanding of the pathways and mechanisms involved in atrial and ventricular arrhythmogenesis.

Evaluation of a novel cardiac signal processing system for electrophysiology procedures: The PURE EP 2.0 study.

BACKGROUND: Intracardiac electrogram data remain one of the primary diagnostic inputs guiding complex ablation procedures. However, the technology to collect, process, and display intracardiac signals has known shortcomings and has not advanced in several decades. OBJECTIVE: The purpose of this study was to evaluate a new signal processing platform, the PURE EP™ system (PURE), in a multi-center, prospective study. METHODS: Intracardiac signal data of clinical interest were collected from 51 patients undergoing ablation procedures with PURE, the signal recording system, and the 3D mapping system at the same time stamps. The samples were randomized and subjected to blinded, controlled evaluation by three independent electrophysiologists to determine the overall quality and clinical utility of PURE signals when compared to conventional sources. Each reviewer assessed the same (92) signal sample sets and responded to (235) questions using a 10-point rating scale. If two or more reviewers rated the PURE signal higher than the control, it was deemed superior. RESULTS: A total of 93% of question responses showed consensus amongst the blinded reviewers. Based on the ratings for each pair of signals, a cumulative total of 164 PURE signals out of 218 (75.2%) were statistically rated as Superior for this data set (p < .001). Only 14 PURE signals out of 218 were rated as Inferior (6.4%). CONCLUSION: The PURE intracardiac signals were statistically rated as superior when compared to conventional systems.

Electrophysiologic testing for diagnostic evaluation and risk stratification in patients with suspected cardiac sarcoidosis with preserved left and right ventricular systolic function.

INTRODUCTION: While cardiac sarcoidosis (CS) carries a risk of ventricular arrhythmias (VAs) and sudden cardiac death (SCD), risk stratification of patients with CS and preserved left ventricular/right ventricular (LV/RV) systolic function remains challenging. We sought to evaluate the role of electrophysiologic testing and programmed electrical stimulation of the ventricle (EPS) in patients with suspected CS with preserved ventricular function. METHODS: One hundred twenty consecutive patients with biopsy-proven extracardiac sarcoidosis and preserved LV/RV systolic function underwent EPS. All patients had either probable CS defined by an abnormal cardiac positron emission tomography or cardiac magnetic resonance imaging, or possible CS with normal advanced imaging but abnormal echocardiogram (ECG), SAECG, Holter, or clinical factors. Patients were followed for 4.5 ± 2.6 years for SCD and VAs. RESULTS: Seven of 120 patients (6%) had inducible ventricular tachycardia (VT) with EPS and received an implantable cardioverter defibrillator (ICD). Three patients (43%) with positive EPS later had ICD therapies for VAs. Kaplan-Meier analysis stratified by EPS demonstrated a significant difference in freedom from VAs and SCD (P = 0.009), though this finding was driven entirely by patients within the cohort with probable CS (P = 0.018, n = 69). One patient with possible CS and negative EPS had unrecognized progression of the disease and unexplained death with evidence of CS at autopsy. CONCLUSIONS: EPS is useful in the risk stratification of patients with probable CS with preserved LV and RV function. A positive EPS was associated with VAs. While a negative EPS appeared to confer low risk, close follow-up is needed as EPS cannot predict fatal VAs related to new cardiac involvement or disease progression.

2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias.

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. An expert writing group, after reviewing and discussing the literature, including a systematic review and meta-analysis published in conjunction with this document, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Each recommendation is presented in knowledge byte format and is accompanied by supportive text and references. Further sections provide a practical synopsis of the various techniques and of the specific ventricular arrhythmia sites and substrates encountered in the electrophysiology lab. The purpose of this document is to help electrophysiologists around the world to appropriately select patients for catheter ablation, to perform procedures in a safe and efficacious manner, and to provide follow-up and adjunctive care in order to obtain the best possible outcomes for patients with ventricular arrhythmias.

Long term follow-up after ventricular tachycardia ablation in patients with congenital heart disease.

BACKGROUND: Ventricular tachycardia (VT) is frequently encountered in patients with repaired and unrepaired congenital heart disease (CHD), causing significant morbidity and sudden cardiac death. Data regarding underlying VT mechanisms and optimal ablation strategies in these patients remain limited. OBJECTIVE: To describe the electrophysiologic mechanisms, ablation strategies, and long-term outcomes in patients with CHD undergoing VT ablation. METHODS: Forty-eight patients (mean age 41.3 ± 13.3 years, 77.1% male) with CHD underwent a total of 57 VT ablation procedures at two centers from 2000 to 2017. Electrophysiologic and follow-up data were analyzed. RESULTS: Of the 77 different VTs induced at initial or repeat ablation, the underlying mechanism in 62 (81.0%) was due to scar-related re-entry; the remaining included four His-Purkinje system-related macrore-entry VTs and focal VTs mainly originating from the outflow tract region (8 of 11, 72.7%). VT-free survival after a single procedure was 72.9% (35 of 48) at a median follow-up of 53 months. VT-free survival after multiple procedures was 85.4% (41 of 48) at a median follow-up of 52 months. There were no major complications. Three patients died during the follow-up period from nonarrhythmic causes, including heart failure and cardiac surgery complication. CONCLUSION: While scar-related re-entry is the most common VT mechanism in patients with CHD, importantly, nonscar-related VT may also be present. In experienced tertiary care centers, ablation of both scar-related and nonscar-related VT in patients with CHD is safe, feasible, and effective over long-term follow-up.

Core isolation of critical arrhythmia elements for treatment of multiple scar-based ventricular tachycardias.

BACKGROUND: Radiofrequency ablation of multiple or unmappable ventricular tachycardias (VTs) remains a challenge with unclear end points. We present our experience with a new strategy isolating core elements of VT circuits. METHODS AND RESULTS: Patients with structural heart disease presenting for VT radiofrequency ablation at 2 centers were included. Strategy involved entrainment/activation mapping if VT was hemodynamically stable, and voltage mapping with electrogram analysis and pacemapping. Core isolation (CI) was performed incorporating putative isthmus and early exit site(s) based on standard criteria. If VT was noninducible, the dense scar (<0.5 mV) region was isolated. Successful CI was defined by exit block (20 mA at 2 ms) within the isolated region. VT inducibility was also assessed. Forty-four patients were included (mean age, 63; 95% male; 73% ischemic cardiomyopathy; mean left ventricular ejection fraction, 31%; 68% with multiple unstable VTs [mean, 3+2]). CI area was 11+12 versus 55+40 cm(2) total scar area. Additional substrate modification was performed in 27 (61%), and epicardial radiofrequency ablation was performed in 4 (9%) patients. CI was achieved in 37 (84%) and led to better VT-free survival (log rank P=0.013). CONCLUSIONS: CI is a novel strategy with a discrete and measurable end point beyond VT inducibility to treat patients with multiple or unmappable VTs. The CI region can be selected based on standard characterization of suspected VT isthmus surrogates thus limiting ablation target size. Exit block within the isolated area is achievable in most and may further improve long-term success.

Layered activation of epicardial scar in arrhythmogenic right ventricular dysplasia: possible substrate for confined epicardial circuits.

BACKGROUND: Ventricular tachycardia ablation in arrhythmogenic right ventricular dysplasia (ARVD) is more successful when including epicardial ablation. Scarring may cause independent, layered epicardial activation and promote epicardially confined ventricular tachycardia circuits. We aimed to characterize transmural right ventricular activation in ARVD patients and to compare this with reference patients without structural heart disease. METHODS AND RESULTS: Eighteen ARVD patients underwent detailed endocardial and epicardial sinus rhythm electroanatomic mapping. Bipolar activation was annotated at the sharpest intrinsic deflection including late potentials and compared with 6 patients with normal hearts. Total scar area was larger on the epicardium (97±78 cm(2)) than the endocardium (57±44 cm(2); P=0.04), with significantly more isolated potentials. Total epicardial activation time was longer than endocardial (172±54 versus 99±27 ms; P<0.01), and both were longer than in reference patients. Earliest endocardial site was the right ventricular anteroseptum in 17 of 18 ARVD patients versus 5 of 6 controls (P=0.446), and latest endocardial site was in the outflow tract in 13 of 18 ARVD patients versus 4 of 6 controls and tricuspid annulus in 5 of 18 ARVD patients versus 2 of 6 controls (P=1.00). In reference patients, epicardial activation directly opposite endocardial sites occurred in 5.2±1.9 ms, suggesting direct transmural activation. In contrast, ARVD patients had major activation delay to the epicardium with laminar central scar activation from the scar border, not by direct transmural spread from the endocardium. CONCLUSIONS: Transmural right ventricular activation is modified by ARVD scarring with a delayed epicardial activation sequence suggestive of independent rather than direct transmural activation. This may predispose ventricular tachycardia circuits contained entirely within the epicardium in ARVD and explains observations on the need for direct epicardial ablation to eliminate ventricular tachycardia.

Is there a relationship between complex fractionated atrial electrograms recorded during atrial fibrillation and sinus rhythm fractionation?

BACKGROUND: Ablation of persistent atrial fibrillation (AF) may require adjunctive methods of substrate modification. Both ablation-targeting complex fractionated atrial electrograms (CFAEs) recorded during AF and fractionated electrograms recorded during sinus rhythm (sinus rhythm fractionation [SRF]) have been described. However, the relationship of CFAEs with SRF is unclear. METHODS: Twenty patients (age 62 ± 9 years, 13 males) with persistent AF and 9 control subjects without organic heart disease or AF (age 36 ± 6 years, 4 males) underwent detailed CFAE and SRF left atrial electroanatomic maps. The overlap in left atrial regions with CFAEs and SRF was compared in the AF population, and the distribution of SRF was compared among patients with AF and normal controls. Propagation maps were analyzed to identify the activation patterns associated with SR fractionation. RESULTS: SRF (338 ± 150 points) and CFAE (418 ± 135 points) regions comprised 29% ± 14% and 25% ± 15% of the left atrial surface area, respectively. There was no significant correlation between SRF and CFAE maps (r = .2; P = NS). On comparing patients with AF and controls, no significant difference was found in the distribution of SRF between groups (P = .74). Regions of SRF overlapped areas of wave-front collision 75% ± 13% of the time. CONCLUSIONS: (1) There is little overlap between regions of CFAEs during AF and regions of SRF measured in the time domain or the frequency domain, (2) the majority of SRF appears to occur in regions with wave-front collision, (3) the distribution of SRF is similar in patients with AF and normal controls, suggesting that this may not have an important role in AF maintenance and may not be a suitable ablation target.

Assessing epicardial substrate using intracardiac echocardiography during VT ablation.

BACKGROUND: Intracardiac echocardiography (ICE) has played a limited role in defining the substrate for ventricular tachycardia (VT). The purpose of this study was to assess whether ICE could identify abnormal epicardial substrate in patients with nonischemic cardiomyopathy (NICM) and VT. METHODS AND RESULTS: We studied 18 patients with NICM and recurrent VT who had abnormal echogenicity identified on ICE imaging. Detailed left ventricular (LV) endocardial and epicardial electroanatomic mapping was performed in all patients. Low-voltage areas (<1.0 mV) in the epicardium were analyzed. ICE imaging in the NICM group was compared to a control group of 30 patients with structurally normal hearts who underwent ICE imaging for other ablation procedures. In 18 patients (age, 53±13 years; 17 men) with NICM (ejection fraction, 37±13%), increased echogenicity was identified in the lateral LV by ICE imaging. LV endocardial electroanatomic mapping identified normal voltage in 9 patients and at least 1 confluent low-voltage area (6.6 cm(2); minimum-maximum, 2.1-31.7 cm(2)) in 9 patients (5 posterolateral LV, 4 perivalvular LV). Detailed epicardial mapping revealed areas of low voltage (39 cm(2); minimum-maximum, 18.5-96.3 cm(2)) and abnormal, fractionated electrograms in all 18 patients (15 posterolateral LV, 3 lateral LV). In all patients, the epicardial scar identified by electroanatomic mapping correlated with the echogenic area identified on ICE imaging. ICE imaging identified no areas of increased echogenicity in the control group. CONCLUSIONS: ICE imaging identified increased echogenicity in the lateral wall of the LV that correlated to abnormal epicardial substrate. These findings suggest that ICE imaging may be useful to identify epicardial substrate in NICM.

Termination of persistent atrial fibrillation during left atrial mapping.

Termination of Persistent AF During Mapping. Complex fractionated atrial electrograms (CFAEs) may represent critical areas for the maintenance of atrial fibrillation (AF). While AF organization and termination have been reported with CFAE ablation, no reports of arrhythmia termination during left atrial mapping exist. We report a case of reproducible AF termination with catheter pressure at a site of CFAE remote from the site of AF.

Isolated septal substrate for ventricular tachycardia in nonischemic dilated cardiomyopathy: incidence, characterization, and implications.

BACKGROUND: The substrate for ventricular tachycardia (VT) in nonischemic cardiomyopathy (NICM) has a predilection for the basolateral left ventricle with right bundle branch block VT morphology. OBJECTIVE: The purpose of this study was to describe a unique group of NICM patients with septal VT substrate. METHODS: Between 1999 and 2010, 31 (11.6%) of 266 patients with NICM undergoing VT ablation had septal substrate and no lateral involvement. Mean age was 59 ± 12 years, and ejection fraction was 30% ± 14%. Eight patients had heart block. RESULTS: Cardiac magnetic resonance showed septal delayed enhancement in 8 of 9 patients. Electroanatomic mapping demonstrated bipolar low voltage (<1.5 mV) extending from the basal septum in 22 of 31 patients. The remaining 9 patients had normal endocardial bipolar voltage but abnormal unipolar septal voltage (<8.3 mV) consistent with intramural abnormalities. Epicardial mapping in 14 patients showed no scar in 9 and patchy basal left ventricular summit scar in 5. VTs were mapped to the septal substrate, with 62% having right bundle branch block morphology and V(2) precordial transition pattern break in 17% suggesting periseptal exit. After substrate and targeted VT ablation, no VT was inducible in 66% and no "clinical targeted" VT in 86%. Over a mean follow-up of 20 ± 28 months, VT recurred in 10 (32%) patients. CONCLUSION: Isolated septal VT substrate is uncommon in NICM. Biventricular low-voltage zones extending from the basal septum are characteristic, but septal scarring can be entirely intramural as evidenced by unipolar/bipolar electrograms and imaging. Multiple unmappable morphologies are the rule, often requiring several procedures aggressively targeting the septal substrate to achieve moderate long-term VT control.

Endocardial unipolar voltage mapping to identify epicardial substrate in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: The risk and success of epicardial substrate ablation for ventricular tachycardia (VT) support the value of techniques identifying the epicardial substrate with endocardial mapping. OBJECTIVE: The purpose of this study was to test the hypothesis that endocardial unipolar voltage mapping in patients with right ventricular (RV) VT and preserved endocardial bipolar voltage abnormalities might identify the extent of epicardial bipolar voltage abnormality. METHODS: Using a cutoff of < 5.5 mV for normal endocardial unipolar voltage derived from 8 control patients without structural heart disease, 10 patients with known ARVC/D (group 1, retrospective) and 13 patients with RV VT (group 2, prospective) with modest or no endocardial bipolar voltage abnormalities underwent detailed endocardial and epicardial mapping. RESULTS: The area of epicardial unipolar voltage abnormality in all 10 group 1 patients with ARVC/D (62 ± 21 cm²) and in 9 of the 13 group 2 patients (8 with criteria for ARVC/D) (53 ± 21 cm²) was on average three times more extensive than the endocardial bipolar abnormality and correlated (r = 0.63, P <.05 and r = 0.81, P <.008, respectively) with the larger area epicardial bipolar abnormality with respect to size (group 1: 82 ± 22 cm²; group 2: 68 ± 41 cm²) and location. In the remaining 4 group 2 patients and 3 additional reference patients without structural heart disease, endocardial bipolar, endocardial unipolar, and, as predicted, epicardial bipolar voltage all were normal. CONCLUSION: Endocardial unipolar mapping with cutoff of 5.5 mV identifies more extensive areas of epicardial bipolar signal abnormalities in patients with ARVC/D and limited endocardial VT substrate.

Endocardial unipolar voltage mapping to detect epicardial ventricular tachycardia substrate in patients with nonischemic left ventricular cardiomyopathy.

BACKGROUND: Patients with nonischemic left ventricular cardiomyopathy (LVCM) and ventricular tachycardia (Vt) have complex 3-dimensional substrate with variable involvement of the endocardium (ENDO) and epicardium (EPI). The purpose of this study was to determine whether ENDO unipolar (UNI) mapping with a larger electric field of view could identify EPI low bipolar (BIP) voltage regions in patients with LVCM undergoing Vt ablation. METHODS AND RESULTS: The reference value for normal ENDO unipolar voltage was determined from 6 patients without structural heart disease. Consecutive patients undergoing Vt ablation over an 8-year period with detailed (>100 points) LV ENDO and EPI mapping and normal LV ENDO BIP voltage were identified. From this cohort, we compared patients with structurally normal hearts and normal EPI BIP voltage (EPI-, group 1) with patients with LVCM and low LV EPI BIP voltage regions present (EPI+, group 2). Confluent regions of ENDO UNI and EPI BIP low voltage (>2 cm(2)) were measured. The normal signal amplitude was >8.27 mV for LV ENDO UNI electrograms. Detailed LV ENDO-EPI maps in 5 EPI- patients were compared with 11 EPI+ patients. Confluent ENDO UNI low-voltage regions were seen in 9 of 11 (82%) of the EPI+ (group 2) patients compared with none of 5 EPI- (group 1) patients (P<0.001). In all 9 patients with ENDO UNI low voltage, the ENDO UNI low-voltage regions were directly opposite to an area of EPI BIP low voltage (61% ENDO UNI-EPI BIP low-voltage area overlap). CONCLUSIONS: EPI arrhythmia substrate can be reliably identified in most patients with LVCM using ENDO UNI voltage mapping in the absence of ENDO BIP abnormalities.