Intracardiac Electrogram Targets for Ventricular Tachycardia Ablation.

The pathogenesis of ventricular tachycardia (VT) in most patients with a prior myocardial scarring is reentry involving compartmentalized muscle fibers protected within the scar. Often the 12-lead ECG morphology of the VT itself is not available when treated with a defibrillator. Consequently, VT ablation takes on an interesting challenge of finding critical targets in sinus rhythm. High-density recordings are essential to evaluate a substrate based on whole electrogram voltage and activation delay, supplemented with substrate perturbation through alternate site pacing or introducing an extra stimulation. In this article, we discuss contemporary intracardiac electrogram targets for VT ablation, with explanation on each of their specific fundamental physiology.

The Role of Artificial Intelligence and Machine Learning in Clinical Cardiac Electrophysiology.

In recent years, numerous applications for artificial intelligence (AI) in cardiology have been found, due in part to large digitized data sets and the evolution of high-performance computing. In the discipline of cardiac electrophysiology (EP), a number of clinical, imaging, and electrical waveform data are considered in the diagnosis, prognostication, and management of arrhythmias, which lend themselves well to automation through AI. But equally relevant, AI offers a unique opportunity to discover novel EP concepts and improve clinical care through its inherent, hierarchical tenets of self-learning. In this review we focus on the application of AI in clinical EP and summarize state-of-the art, large, clinical studies in the following key domains: (1) electrocardiogram-based arrhythmia and disease classification; (2) atrial fibrillation source detection; (3) substrate and risk assessment for atrial fibrillation and ventricular tachyarrhythmias; and (4) predicting outcomes after cardiac resynchronization therapy. Many are small, single-centre, proof-of-concept investigations, but they still show ground-breaking performance of deep learning, a subdomain of AI, which surpasses traditional statistical analysis. Larger studies, for instance classifying arrhythmias from electrocardiogram recordings, have further provided external validation of their high accuracy. Ultimately, the performance of AI is dependent on the quality of the input data and the rigour of algorithm development. The field is still nascent and several barriers will need to be overcome, including prospective validation in large, well labelled data sets and more seamless information technology-based data collection/integration, before AI can be adopted into broader clinical EP practice. This review concludes with a discussion of these challenges and future work.

Prophylactic anticoagulation in sinus rhythm for stroke prevention in cardiovascular disease: contemporary meta-analysis of large randomized trials.

AIMS: Anticoagulation with non-vitamin K oral anticoagulants (NOACs) to prevent stroke is a mainstay of atrial fibrillation (AF) management. However, multiple cardiovascular diseases (CVDs) are associated with elevated ischaemic stroke risk even in sinus rhythm. In this meta-analysis, we assess efficacy and safety of prophylactic NOAC agents for stroke prevention in patients without AF. METHODS AND RESULTS: A search was conducted for randomized controlled trials (RCTs) that evaluated an NOAC and control drug (placebo or antiplatelet) in non-AF patients with mixed CVD. The primary efficacy and safety outcomes were ischaemic stroke and major bleeding, respectively. Results were stratified based on primary- and mini-NOAC doses. Thirteen RCTs were identified with a total of 89 383 patients with CVD in sinus rhythm (53 778 on NOAC, 35 605 on control drug; mean age 65.5 ± 2.7 years). Over a mean follow-up of 18.3 months, 1429 (1.6%) ischaemic strokes occurred. Use of NOAC was associated with 26% reduction in stroke [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.62-0.87; 1.1 vs. 1.8 events per 100 person-years], with numbers needed to treat of 153 patients to prevent one stroke. Major bleeding was increased with NOAC (OR 1.74, 95% CI 1.44-2.09; 2.1 vs. 1.0 events per 100 person-years). The weighted net clinical benefit (wNCB, composite of ischaemic stroke and bleeding) did not suggest a favourable effect with any NOAC dose (wNCB for primary-dose: -0.35; mini-dose: -0.06). CONCLUSION: Current evidence does not support use of NOACs for stroke prevention in non-AF CVD population as risk of major bleeding still exceeds ischaemic stroke benefit.

Deep Learning Classification of Unipolar Electrograms in Human Atrial Fibrillation: Application in Focal Source Mapping.

Focal sources are potential targets for atrial fibrillation (AF) catheter ablation, but they can be time-consuming and challenging to identify when unipolar electrograms (EGM) are numerous and complex. Our aim was to apply deep learning (DL) to raw unipolar EGMs in order to automate putative focal sources detection. We included 78 patients from the Focal Source and Trigger (FaST) randomized controlled trial that evaluated the efficacy of adjunctive FaST ablation compared to pulmonary vein isolation alone in reducing AF recurrence. FaST sites were identified based on manual classification of sustained periodic unipolar QS EGMs over 5-s. All periodic unipolar EGMs were divided into training (n = 10,004) and testing cohorts (n = 3,180). DL was developed using residual convolutional neural network to discriminate between FaST and non-FaST. A gradient-based method was applied to interpret the DL model. DL classified FaST with a receiver operator characteristic area under curve of 0.904 ± 0.010 (cross-validation) and 0.923 ± 0.003 (testing). At a prespecified sensitivity of 90%, the specificity and accuracy were 81.9 and 82.5%, respectively, in detecting FaST. DL had similar performance (sensitivity 78%, specificity 89%) to that of FaST re-classification by cardiologists (sensitivity 78%, specificity 79%). The gradient-based interpretation demonstrated accurate tracking of unipolar QS complexes by select DL convolutional layers. In conclusion, our novel DL model trained on raw unipolar EGMs allowed automated and accurate classification of FaST sites. Performance was similar to FaST re-classification by cardiologists. Future application of DL to classify FaST may improve the efficiency of real-time focal source detection for targeted AF ablation therapy.

Safety, efficacy, and monitoring of bipolar radiofrequency ablation in beating myopathic human and healthy swine hearts.

BACKGROUND: The safety and efficacy parameters for bipolar radiofrequency (RF) ablation are not well defined. OBJECTIVE: The purpose of this study was to investigate the safe range of power, utility of transmyocardial bipolar electrogram (EGM) amplitude, and circuit impedance in ablation monitoring. METHODS: Sixteen beating ex vivo human and swine hearts were studied in a Langendorff setup. Ninety-two bipolar ablations using two 4-mm irrigated catheters were performed at settings of 20-50 W, 60 seconds, and 30 mL/min irrigation in the left ventricle. RESULTS: For low-power ablations (20 and 30 W), transmurality was observed in 29 of 38 (76%) and 10 of 28 (36%) ablations for tissue thickness ≤17 mm and >17 mm, respectively. For high-power ablations (40 and 50 W), transmurality was observed in 5 of 7 (71%) and 7 of 19 (37%) ablations for tissue thickness ≤17 mm and >17 mm, respectively. Steam pop occurrence for low- and high-power ablations was 11 of 66 (16%) and 16 of 26 (62%), respectively (P = .0001), respectively. Lesion depth (limited by transmurality) was 12.0 ± 5.7 mm and 12.3 ± 5.8 mm, respectively (P = 1). Transmyocardial EGM amplitude decrement >60% strongly predicted transmurality (area under the curve [AUC] 0.8), and circuit impedance decrement >26% predicted steam pops (AUC 0.75). Half-normal saline did not affect transmurality or incidence of steam pops compared to normal saline irrigation. CONCLUSION: Bipolar RF ablation at power of 20-30 W provided an ideal balance of safety and efficacy, whereas power ≥40 W should be used with caution due to the high incidence of steam pops. Lesion transmurality monitoring and steam pop avoidance were best achieved using transmyocardial bipolar EGM voltage and circuit impedance, respectively.

Unipolar electrogram-based voltage mapping with far-field cancellation to improve detection of abnormal atrial substrate during atrial fibrillation.

INTRODUCTION: An important substrate for atrial fibrillation (AF) is fibrotic atrial myopathy. Identifying low voltage, myopathic regions during AF using traditional bipolar voltage mapping is limited by the directional dependency of wave propagation. Our objective was to evaluate directionally independent unipolar voltage mapping, but with far-field cancellation, to identify low-voltage regions during AF. METHODS: In 12 patients undergoing pulmonary vein isolation for AF, high-resolution voltage mapping was performed in the left atrium during sinus rhythm and AF using a roving 20-pole circular catheter. Bipolar electrograms (EGMs) (Bi) < 0.5 mV in sinus rhythm identified low-voltage regions. During AF, bipolar voltage and unipolar voltage maps were created, the latter with (uni-res) and without (uni-orig) far-field cancellation using a novel, validated least-squares algorithm. RESULTS: Uni-res voltage was ~25% lower than uni-orig for both low voltage and normal atrial regions. Far-field EGM had a dominant frequency (DF) of 4.5-6.0 Hz, and its removal resulted in a lower DF for uni-orig compared with uni-res (5.1 ± 1.5 vs. 4.8 ± 1.5 Hz; p < .001). Compared with Bi, uni-res had a significantly greater area under the receiver operator curve (0.80 vs. 0.77; p < .05), specificity (86% vs. 76%; p < .001), and positive predictive value (43% vs. 30%; p < .001) for detecting low-voltage during AF. Similar improvements in specificity and positive predictive value were evident for uni-res versus uni-orig. CONCLUSION: Far-field EGM can be reliably removed from uni-orig using our novel, least-squares algorithm. Compared with Bi and uni-orig, uni-res is more accurate in detecting low-voltage regions during AF. This approach may improve substrate mapping and ablation during AF, and merits further study.

Focal and pseudo/rotational activations in human atrial fibrillation defined with automated periodicity mapping.

INTRODUCTION: Defining atrial fibrillation (AF) wave propagation is challenging unless local signal features are discrete or periodic. Periodic focal or rotational activity may identify AF drivers. Our objective was to characterize AF propagation at sites with periodic activation to evaluate the prevalence and relationship between focal and rotational activation. METHODS: We included 80 patients (61 ± 10 years, persistent AF 49%) from the FaST randomized trial that compared the efficacy of adjunctive focal site ablation versus pulmonary vein isolation. Patients underwent left atrial (LA) activation mapping with a 20-pole circular catheter during spontaneous or induced AF. Five-second bipolar and unipolar electrograms in AF were analyzed. Periodic sites were identified by spectral analysis of the bipolar electrogram. Activation maps of periodic sites were constructed using an automated, validated tracking algorithm, and classified into three patterns: focal sites (FS), rotation (RO), or pseudo-rotation (pRO). RESULTS: The most common propagation pattern at periodic sites was FS for 5-s in all patients (4.9 ± 1.9 per patient). RO and pRO were observed in two and seven patients, respectively, but were all transient (3-5 cycles). Activation from a FS evolved into transient RO/pRO in five patients. No patient had autonomous RO/pRO activations. Patients with RO/pRO had greater LA surface area with periodicity (78 ± 7 vs. 63 ± 16%, p = .0002) and shorter LA periodicity CL (166 ± 10 vs. 190±28 ms, p = .0001) than the rest. CONCLUSION: Using automated, regional AF periodicity mapping, FS is more prevalent and temporally stable than RO/pRO. Most RO/pRO evolve from neighboring FS. These findings and their implications for AF maintenance require verification with global, panoramic mapping.

Microvolt QRS Alternans Without Microvolt T-Wave Alternans in Human Cardiomyopathy: A Novel Risk Marker of Late Ventricular Arrhythmias.

Background Action potential alternans can induce ventricular tachyarrhythmias and manifest on the surface ECG as T-wave alternans (TWA) and QRS alternans (QRSA). We sought to evaluate microvolt QRSA in cardiomyopathy patients in relation to TWA and ventricular tachyarrhythmia outcomes. Methods and Results Prospectively enrolled cardiomyopathy patients (n=100) with prophylactic defibrillators had 12-lead ECGs recorded during ventricular pacing from 100 to 120 beats/min. QRSA and TWA were quantified in moving 128-beat segments using the spectral method. Segments were categorized as QRSA positive (QRSA+) and/or TWA positive (TWA+) based on ≥2 precordial leads having alternans magnitude >0 and signal:noise >3. Patients were similarly categorized based on having ≥3 consecutive segments with alternans. TWA+ and QRSA+ occurred together in 31% of patients and alone in 18% and 14% of patients, respectively. Although TWA magnitude (1.4±0.4 versus 4.7±1.0 µV, P<0.01) and proportion of TWA+ studies (16% versus 46%, P<0.01) increased with rate, QRSA did not change. QRS duration was longer in QRSA+ than QRSA-negative patients (138±23 versus 113±26 ms, P<0.01). At 3.5 years follow-up, appropriate defibrillator therapy or sustained ventricular tachyarrhythmia was greater in QRSA+ than QRSA-negative patients (30% versus 8%, P=0.02) but similar in TWA+ and TWA-negative patients. Among QRSA+ patients, the event rate was greater in those without TWA (62% versus 21%, P=0.02). Multivariable Cox analysis revealed QRSA+ (hazard ratio [HR], 4.6; 95% CI, 1.5-14; P=0.009) and QRS duration >120 ms (HR, 4.1; 95% CI, 1.3-12; P=0.014) to predict events. Conclusions Microvolt QRSA is novel phenomenon in cardiomyopathy patients that can exist without TWA and is associated with QRS prolongation. QRSA increases the risk of ventricular tachyarrhythmia 4-fold, which merits further study as a risk stratifier.

Signature signal strategy: Electrogram-based ventricular tachycardia mapping.

Multiple decades of work have recognized complexities of substrates responsible for ventricular tachycardia (VT). There is sufficient evidence that 3 critical components of a re-entrant VT circuit, namely, region of slow conduction, zone of unidirectional block, and exit site, are located in spatial vicinity to each other in the ventricular scar. Each of these components expresses characteristic electrograms in sinus rhythm, at initiation of VT, and during VT, respectively. Despite this, abnormal electrograms are widely targeted without appreciation of these signature electrograms during contemporary VT ablation. Our aim is to stimulate physiology-based VT mapping and a targeted ablation of VT. In this article, we focus on these 3 underappreciated aspects of the physiology of ischemic scar-related VT circuits that have practical applications during a VT ablation procedure. We explore the anatomic and functional elements underlying these distinctive bipolar electrograms, specifically the contribution of tissue branching, conduction restitution, and wave curvature to the substrate, as they pertain to initiation and maintenance of VT. We propose a VT ablation approach based on these 3 electrogram features that can be a potential practical means to recognize critical elements of a VT circuit and target ablation.

Focal source and trigger mapping in atrial fibrillation: Randomized controlled trial evaluating a novel adjunctive ablation strategy.

BACKGROUND: Intraoperative mapping has demonstrated focal activations during human atrial fibrillation (AF). These putative AF sources can manifest sustained periodic bipolar and unipolar QS electrograms (EGMs). We have automated the detection of these EGM features using our validated Focal Source and Trigger (FaST) computational algorithm. OBJECTIVE: The purpose of this study was to conduct a randomized controlled pilot evaluating the feasibility and efficacy of FaST mapping/ablation as an adjunct to pulmonary vein isolation (PVI) in reducing AF recurrence. METHODS: We randomized 80 patients with high-burden paroxysmal or persistent AF (age 61 ± 10 years; 75% male) to PVI alone (n = 41) or PVI+FaST mapping/ablation (n = 39). The primary endpoint was time to AF recurrence >30 seconds between 3 and 12 months after 1 procedure. RESULTS: FaST sites were identified in all but 1 patient and were localized to pulmonary vein (PV) (2.1 ± 1.1 per patient) and extra-PV regions (2.8 ± 1.4 per patient). FaST mapping and ablation times were 27 ± 9 minutes and 8.5 ± 5 minutes, respectively. Patients with AF termination during ablation had greater AF cycle length prolongation with PVI+FaST than PVI (Δ20 ± 14 ms vs Δ5 ± 17 ms; P = .046). Freedom from AF recurrence at 12 months was higher in PVI+FaST vs PVI for patients off antiarrhythmic drugs (74% vs 51%; hazard ratio 0.48; 95% confidence interval 0.21-1.08; P = .064) but did not quite reach statistical significance. Major adverse events were similar between the 2 groups. CONCLUSION: In this randomized controlled pilot, real-time FaST mapping provided an intuitive, automated approach for localizing focal AF sources. FaST ablation as an adjunct to PVI may reduce AF recurrence, which requires verification with a larger multicenter trial.

Lateral tunnel Fontan atrial tachycardia ablation trans-baffle access is not mandatory as the initial strategy.

BACKGROUND: Mapping and ablation of atrial tachycardia (AT) is commonly performed in lateral tunnel Fontan (LTF) patients, yet there is little information on the need of baffle puncture to access the pulmonary venous atrium (PVA). This study aimed to evaluate the most common chamber location of critical sites for majority of AT in LTF patients. METHODS: Consecutive LTF patients underwent catheter-based high-density mapping and ablation of AT from Nov. 2015 to Mar. 2019. Critical sites were identified by a combination of activation and entrainment mapping. Acute procedural success was defined as AT termination with ablation and non-inducibility of any AT. Predictors for ablation failure were evaluated in retrospect. RESULTS: Fifteen catheter ablation procedures were performed in 9 patients. A total of 15 clinical ATs (mean TCL 369 ± 91 ms) were mapped. The mechanism was macro re-entry in 11 (73%) and micro re-entry in 2. In 11 ATs (73%), 94 ± 5% of tachycardia cycle length (TCL) were mapped inside the tunnel. The commonest site of successful ablation in the tunnel was on the lateral wall (60%). Trans-baffle access was obtained during 5 of 15 procedures (33%). Overall, procedural success was achieved in 9 of 15 procedures (60%). There were no complications. Recurrence of AT was 42% over a follow-up period of 4.3 ± 3.2 years. Faster TCL of 200-300 ms showed a trend towards ablation failure, (OR 17, 95% CI 0.7 to 423, p = 0.08). CONCLUSIONS: Catheter ablation can be performed effectively for ATs in LTF patients usually from inside the tunnel. ATs with critical sites in the PVA are uncommon. This information will help plan ablation in LTF patients without resorting to initial trans-baffle access.

Direct and indirect mapping of intramural space in ventricular tachycardia.

BACKGROUND: The ventricular tachycardia (VT) circuit is often assumed to be located in the endocardium or epicardium. The plateauing success rate of VT ablation warrants reevaluation of this mapping paradigm. OBJECTIVE: The purpose of this study was to resolve the intramural components of VT circuits by mapping in human hearts. METHODS: Panoramic simultaneous endocardial-epicardial mapping (SEEM) during intraoperative mapping (IOM) was performed in human subjects. In explanted hearts (EH), SEEM and intramural multielectrode plunge needle mapping (NM) of the left ventricle were performed. Overall, 37 VTs (26 ischemic cardiomyopathy [ICM], 11 nonischemic cardiomyopathy [NICM]) were studied in 32 patients. Intraoperative SEEM was performed in 16 patients (16 ICM). Additionally, 16 explanted myopathic human hearts (9 NICM, 7 ICM) were studied in a Langendorff setup. Predominant intramural location of the VT was imputed by the absence of significant endocardial-epicardial activation during IOM (using SEEM and no NM) or by the presence of intramural activation spanning the entire cycle length (including mid-diastole) in EH (SEEM and NM). RESULTS: By IOM (SEEM), predominant endocardial activation (entire tachycardia cycle length including mid-diastolic activation) was present in 10 of 18 VTs (55%). In 8 of 18 VTs (44%), the VT circuit was presumed to be intramural due to incomplete diastolic activation in endocardium and epicardium. In EH (SEEM and NM), VT location was predominantly intramural, endocardial, and epicardial in 8 of 19 (42%), 5 of 19 (26%), and 1 of 19 VTs (5%), respectively. CONCLUSION: In a significant proportion of both ischemic and nonischemic ventricular tachycardias, the predominant activation was located in the intramural space.

Quantification of abnormal QRS peaks predicts response to cardiac resynchronization therapy and tracks structural remodeling.

BACKGROUND: Although QRS duration (QRSd) is an important determinant of cardiac resynchronization therapy (CRT) response, non-responder rates remain high. QRS fragmentation can also reflect electrical dyssynchrony. We hypothesized that quantification of abnormal QRS peaks (QRSp) would predict CRT response. METHODS: Forty-seven CRT patients (left ventricular ejection fraction = 23±7%) were prospectively studied. Digital 12-lead ECGs were recorded during native rhythm at baseline and 6 months post-CRT. For each precordial lead, QRSp was defined as the total number of peaks detected on the unfiltered QRS minus those detected on a smoothed moving average template QRS. CRT response was defined as >5% increase in left ventricular ejection fraction post-CRT. RESULTS: Sixty-percent of patients responded to CRT. Baseline QRSd was similar in CRT responders and non-responders, and did not change post-CRT regardless of response. Baseline QRSp was greater in responders than non-responders (9.1±3.5 vs. 5.9±2.2, p = 0.001) and decreased in responders (9.2±3.6 vs. 7.9±2.8, p = 0.03) but increased in non-responders (5.5±2.3 vs. 7.5±2.8, p = 0.049) post-CRT. In multivariable analysis, QRSp was the only independent predictor of CRT response (Odds Ratio [95% Confidence Interval]: 1.5 [1.1-2.1], p = 0.01). ROC analysis revealed QRSp (area under curve = 0.80) to better discriminate response than QRSd (area under curve = 0.67). Compared to QRSd ≥150ms, QRSp ≥7 identified response with similar sensitivity but greater specificity (74 vs. 32%, p<0.05). Amongst patients with QRSd <150ms, more patients with QRSp ≥7 responded than those with QRSp <7 (75 vs. 0%, p<0.05). CONCLUSIONS: Our novel automated QRSp metric independently predicts CRT response and decreases in responders. Electrical dyssynchrony assessed by QRSp may improve CRT selection and track structural remodeling, especially in those with QRSd <150ms.

Omnipolarity applied to equi-spaced electrode array for ventricular tachycardia substrate mapping.

AIMS: Bipolar electrogram (BiEGM)-based substrate maps are heavily influenced by direction of a wavefront to the mapping bipole. In this study, we evaluate high-resolution, orientation-independent peak-to-peak voltage (Vpp) maps obtained with an equi-spaced electrode array and omnipolar EGMs (OTEGMs), measure its beat-to-beat consistency, and assess its ability to delineate diseased areas within the myocardium compared against traditional BiEGMs on two orientations: along (AL) and across (AC) array splines. METHODS AND RESULTS: The endocardium of the left ventricle of 10 pigs (three healthy and seven infarcted) were each mapped using an Advisor™ HD grid with a research EnSite Precision™ system. Cardiac magnetic resonance images with late gadolinium enhancement were registered with electroanatomical maps and were used for gross scar delineation. Over healthy areas, OTEGM Vpp values are larger than AL bipoles by 27% and AC bipoles by 26%, and over infarcted areas OTEGM Vpp values are 23% larger than AL bipoles and 27% larger than AC bipoles (P < 0.05). Omnipolar EGM voltage maps were 37% denser than BiEGM maps. In addition, OTEGM Vpp values are more consistent than bipolar Vpps showing less beat-by-beat variation than BiEGM by 39% and 47% over both infarcted and healthy areas, respectively (P < 0.01). Omnipolar EGM better delineate infarcted areas than traditional BiEGMs from both orientations. CONCLUSION: An equi-spaced electrode grid when combined with omnipolar methodology yielded the largest detectable bipolar-like voltage and is void of directional influences, providing reliable voltage assessment within infarcted and non-infarcted regions of the heart.