Heterogeneous repolarization creates ventricular tachycardia circuits in healed myocardial infarction scar.

Arrhythmias originating in scarred ventricular myocardium are a major cause of death, but the underlying mechanism allowing these rhythms to exist remains unknown. This gap in knowledge critically limits identification of at-risk patients and treatment once arrhythmias become manifest. Here we show that potassium voltage-gated channel subfamily E regulatory subunits 3 and 4 (KCNE3, KCNE4) are uniquely upregulated at arrhythmia sites within scarred myocardium. Ventricular arrhythmias occur in areas with a distinctive cardiomyocyte repolarization pattern, where myocyte tracts with short repolarization times connect to myocytes tracts with long repolarization times. We found this unique pattern of repolarization heterogeneity only in ventricular arrhythmia circuits. In contrast, conduction abnormalities were ubiquitous within scar. These repolarization heterogeneities are consistent with known functional effects of KCNE3 and KCNE4 on the slow delayed-rectifier potassium current. We observed repolarization heterogeneity using conventional cardiac electrophysiologic techniques that could potentially translate to identification of at-risk patients. The neutralization of the repolarization heterogeneities could represent a potential strategy for the elimination of ventricular arrhythmia circuits.

Nonsustained Ventricular Tachycardia Is Independently Associated With Sustained Ventricular Arrhythmias in Nonischemic Dilated Cardiomyopathy.

BACKGROUND: Spontaneous nonsustained ventricular tachycardia (NSVT) on Holter, VT inducibility during electrophysiology study, and late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) have been associated with sustained ventricular arrhythmias (SVAs) in nonischemic dilated cardiomyopathy (DCM). This study aimed to analyze whether these parameters carry independent prognostic value for spontaneous SVA in DCM. METHODS: Between 2011 and 2018, patients with the DCM clinical spectrum and documented SVA, suspected SVA, or considered to be at intermediate or high risk for SVA were enrolled in the prospective Leiden Nonischemic Cardiomyopathy Study. Patients underwent a comprehensive evaluation including 24-hour Holter, LGE-CMR, and electrophysiology study. Holters were assessed for the presence of NSVT (≥3 beats; rate, ≥120 bpm; lasting <30 s) and NSVT characteristics (coupling interval, duration, cycle length, morphology, regularity). Patients were followed at 6 to 12 monthly intervals. RESULTS: Of all 115 patients (age, 59±12 years; 77% men; left ventricular ejection fraction, 33±13%; history of SVA, 36%; LGE in 63%; median LGE mass, 13 g; interquartile range, 8-23 g), 62 (54%) had NSVT on Holter, and sustained monomorphic VT was inducible in 34 of 114 patients (30%). NSVT was not associated with LGE on CMR or VT inducibility during electrophysiology study nor were its features (all P>0.05). During 4.0±1.8 years of follow-up, SVA occurred in 39 patients (34%). NSVT (HR, 4.47 [95% CI, 1.87-10.72]; P=0.001) and VT inducibility (HR, 3.08 [95% CI, 1.08-8.81]; P=0.036) were independently associated with SVA during follow-up. A bivariable model including only noninvasively acquired parameters also allowed identification of a high-risk subgroup (ie, those with both NSVT and LGE on CMR). The findings remained similar when only patients without prior SVA were included. CONCLUSIONS: In patients with DCM, NSVT on Holter and VT inducibility during electrophysiology study predict SVA during follow-up independent of LGE on CMR. NSVTs may serve as an initiator, and sustained VT inducibility indicates the presence of the substrate for SVA in DCM. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01940081.

Structure and function of the ventricular tachycardia isthmus.

Catheter ablation of postinfarction reentrant ventricular tachycardia (VT) has received renewed interest owing to the increased availability of high-resolution electroanatomic mapping systems that can describe the VT circuits in greater detail, and the emergence and need to target noninvasive external beam radioablation. These recent advancements provide optimism for improving the clinical outcome of VT ablation in patients with postinfarction and potentially other scar-related VTs. The combination of analyses gleaned from studies in swine and canine models of postinfarction reentrant VT, and in human studies, suggests the existence of common electroanatomic properties for reentrant VT circuits. Characterizing these properties may be useful for increasing the specificity of substrate mapping techniques and for noninvasive identification to guide ablation. Herein, we describe properties of reentrant VT circuits that may assist in elucidating the mechanisms of onset and maintenance, as well as a means to localize and delineate optimal catheter ablation targets.

Ventricular arrhythmias in athletes: Role of a comprehensive diagnostic workup.

BACKGROUND: Ventricular arrhythmias (VAs) represent a critical issue with regard to sports eligibility assessment in athletes. The ideal diagnostic evaluation of competitive and leisure-time athletes with complex VAs has not been clearly defined. OBJECTIVE: The purpose of this study was to assess the clinical implications of invasive electrophysiological assessments and endomyocardial biopsy (EMB) among athletes with VAs. METHODS: We evaluated 227 consecutive athletes who presented to our institutions after being disqualified from participating in sports because of VAs. After noninvasive tests, electrophysiological study (EPS), electroanatomic mapping (EAM), and EAM- or cardiac magnetic resonance imaging-guided EMB was performed, following a prespecified protocol. Sports eligibility status was redefined at 6-month follow-up. RESULTS: From our sample, 188 athletes (82.8%) underwent EAM and EPS, and 42 (15.2%) underwent EMB. A diagnosis of heart disease could be formulated in 30% of the study population (67/227; 95% confidence interval [CI] 0.24-0.36) after noninvasive tests; in 37% (83/227; 95% CI 31%-43%) after EPS and EAM; and in 45% (102/227; 95% CI 39%-51%) after EMB. In the subset of athletes undergoing EMB, invasive diagnostic workup allowed diagnostic reclassification of half of the athletes (n = 21 [50%]). Reclassification was particularly common among subjects without definitive findings after noninvasive evaluation (n = 23; 87% reclassified). History of syncope, abnormal echocardiogram, presence of late gadolinium enhancement, and abnormal EAM were linked to sports ineligibility at 6-month follow-up. CONCLUSION: A comprehensive invasive workup provided additional diagnostic elements and could improve the sports eligibility assessment of athletes presenting with VAs. The extensive invasive evaluation presented could be especially helpful when noninvasive tests show unclear findings.

Rotational Activation Pattern During Functional Substrate Mapping: Novel Target for Catheter Ablation of Scar-Related Ventricular Tachycardia.

BACKGROUND: Recent advancements in a 3-dimensional mapping system allow for the assessment of detailed conduction properties during sinus rhythm and thus the establishment of a strategy targeting functionally abnormal regions in scar-related ventricular tachycardia (VT). We hypothesized that a rotational activation pattern (RAP) observed in maps during baseline rhythm was associated with the critical location of VT. METHODS: We retrospectively examined the pattern of wavefront propagation during sinus rhythm in patients with scar-related VT. The prevalence and features of the RAP on critical VT circuits were analyzed. RAP was defined as >90° of inward curvature directly above or at the edge of the slow conductive areas. RESULTS: Forty-five VTs in 37 patients (66±15 years old, 89% male, 27% ischemic heart disease) were evaluated. High-density substrate mapping during sinus rhythm (median, 2524 points) was performed using the CARTO3 system before VT induction. Critical sites for reentry were identified by direct termination by radiofrequency catheter ablation in 21 VTs or by pace mapping in 12 VTs. Among them, RAP was present in 70% of the 33 VTs. Four VTs had no RAP at the critical sites during sinus rhythm, but it became visible in the mappings with different wavefront directions. Six VTs, in which intramural or epicardial isthmus was suspected, were rendered noninducible by radiofrequency catheter ablation to the endocardial surface without RAP. RAP had a sensitivity and specificity of 70% and 89%, respectively, for predicting the elements in the critical zone for VT. CONCLUSIONS: The critical zone of VT appears to correspond to an area characterized by the RAP with slow conduction during sinus rhythm, which facilitates targeting areas specific for reentry. However, this may not be applicable to intramural VT substrates and might be affected by the direction of wavefront propagation to the scar during mapping. Graphic Abstract: A graphic abstract is available for this article.

Substrate Characterization and Outcome of Catheter Ablation of Ventricular Tachycardia in Patients With Nonischemic Cardiomyopathy and Isolated Epicardial Scar.

BACKGROUND: The substrate for ventricular tachycardia (VT) in left ventricular (LV) nonischemic cardiomyopathy may be epicardial. We assessed the prevalence, location, endocardial electrograms, and VT ablation outcomes in LV nonischemic cardiomyopathy with isolated epicardial substrate. METHODS: Forty-seven of 531 (9%) patients with LV nonischemic cardiomyopathy and VT demonstrated normal endocardial (>1.5 mV)/abnormal epicardial bipolar low-voltage area (LVA, <1.0 mV and signal abnormality). Abnormal endocardial unipolar LVA (≤8.3 mV) and endocardial bipolar split electrograms and predictors of ablation success were assessed. RESULTS: Epicardial bipolar LVA (27.3 cm2 [interquartile range, 15.8-50.0]) localized to basal (40), mid (8), and apical (3) LV with basal inferolateral LV most common (28/47, 60%). Of 44 endocardial maps available, 40 (91%) had endocardial unipolar LVA (24.5 cm2 [interquartile range, 9.4-68.5]) and 29 (67%) had characteristic normal amplitude endocardial split electrograms opposite the epicardial LVA. At mean of 34 months, the VT-free survival was 55% after one and 72% after multiple procedures. Greater endocardial unipolar LVA than epicardial bipolar LVA (hazard ratio, 10.66 [CI, 2.63-43.12], P=0.001) and number of inducible VTs (hazard ratio, 1.96 [CI, 1.27-3.00], P=0.002) were associated with VT recurrence. CONCLUSIONS: In patients with LV nonischemic cardiomyopathy and VT, the substrate may be confined to epicardial and commonly basal inferolateral. LV endocardial unipolar LVA and normal amplitude bipolar split electrograms identify epicardial LVA. Ablation targeting epicardial VT and substrate achieves good long-term VT-free survival. Greater endocardial unipolar than epicardial bipolar LVA and more inducible VTs predict VT recurrence.

Electrocardiographic and electrophysiological characteristics of idiopathic ventricular arrhythmias with acute successful ablation at the superior portion of the mitral annulus.

BACKGROUND: We sought to identify the electrocardiographic and electrophysiological characteristics of ventricular arrhythmias (VAs), including idiopathic ventricular tachycardia (VT) and premature ventricular contractions (PVCs), with acute successful radiofrequency catheter ablation (RFCA) at the superior portion of the mitral annulus (SP-MA). METHODS AND RESULTS: Among 437 consecutive patients who presented with VAs for RFCA, twenty-six patients with acute successful RFCA at the SP-MA were included in this study. The ratio of the amplitude of the first positive peak (if present) versus the nadir in the unipolar electrogram (EGM) was 0.00-0.03 (0.00) at the acute successful RFCA site. The time interval between the QRS onset and the maximum descending slope (D-Max) in the unipolar EGM (QRS-Uni) was 18.8 ± 13.6 ms. With bipolar mapping, the ventricular QRS (V-QRS) interval was 3.75-17.3 (11) ms, 6 (23.1%) patients showed the earliest V-QRS interval of 0 ms, and the other 20 patients (76.9%) showed a V-QRS interval of 10-54 ms. The RFCA start-to-effect time was 14.1 ± 7.2 s in 23 patients (88.5%). In the remaining 3 patients (11.5%), the mean duration of successful RFCA was not well defined due to the infrequent nature of clinical VAs during RFCA. Early (within 3 days) and late (1-year) recurrence rates were 23.1% (6 patients) and 26.9% (7 patients), respectively. VAs disappeared 3 days later due to delayed RFCA efficacy in 2 patients (7.7%). No complications occurred during the RFCA procedure or the one-year follow-up. CONCLUSIONS: SP-MA VAs are a rare but distinct subgroup of VAs. Bipolar and unipolar EGM features can help to determine the optimal RFCA site, and the QRS-Uni interval may serve as a marker that could be used to guide RFCA.

Ventricular arrhythmias ablated successfully in the subvalvular interleaflet triangle between the right and left coronary cusps: Electrophysiological characteristics and catheter ablation.

BACKGROUND: Ventricular arrhythmias (VAs) ablated successfully at the right-left subvalvular interleaflet triangle (R-L ILT) between right and left coronary cusps have not been fully characterized. OBJECTIVE: The purpose of this study was to investigate the electrophysiological characteristics of these VAs and their relationships with the left ventricular (LV) summit. METHODS: Twenty-eight VAs ablated successfully at the R-L ILT were studied. RESULTS: Ninety-six percent of VAs had an early precordial electrocardiographic transition. R-wave amplitude in lead V1 was relatively high (RS morphology, R-wave amplitude 0.35 ± 0.09 mV; R/S ratio 0.35 ± 0.27), whereas the morphology of lead I was R-shaped in 71% and M-shaped in 50% of VAs. Earliest potential was recorded at the R-L ILT in 13 of 28 patients and the left pulmonary sinus cusp (LC) in 6 of 28 patients. Mapping the summit communicating vein (summit-CV) failed because of anatomic or instrumental limitations in these 19 patients. In the other 9 patients, earliest potential was successfully recorded at the summit-CV, while perfect pacemapping was achieved. Poor pace mapping was achieved at the R-L ILT or LC in most patients (27/28). Target site was located at the top of the R-L ILT in all cases. A presystolic potential was present at the target site in 18 of 28 patients. A U-curve via the retrograde method was conventionally used to reach the top of the R-L ILT. CONCLUSION: VAs ablated successfully at the R-L ILT have unique electrophysiological characteristics, and R-L ILT may be an endocardial anatomic ablation target for VAs originating from the base of the LV summit.

Radiofrequency Ablation Strategies for Intramural Ventricular Arrhythmias.

Catheter ablation is an established treatment strategy for ventricular arrhythmias. However, the presence of intramural substrate poses challenges with mapping and delivery of radiofrequency energy, limiting overall success of catheter ablation. Advances over the past decade have improved our understanding of intramural substrate and paved the way for innovative treatment approaches. Modifications in catheter ablation techniques and development of novel ablation technologies have led to improved clinical outcomes for patients with ventricular arrhythmias. In this review, we explore mapping techniques to identify intramural substrate and describe available radiofrequency energy delivery techniques that can improve overall success rates of catheter ablation.

Coronary Venous Mapping and Catheter Ablation for Ventricular Arrhythmias.

Catheter ablation is an effective treatment method for ventricular arrhythmias (VAs). These arrhythmias can often be mapped and targeted with ablation from the left and right ventricular endocardium. However, in some situations the VA site of origin or substrate may be intramural or epicardial in nature. In these cases, the coronary venous system (CVS) provides an effective vantage point for mapping and ablation. This review highlights situations in which CVS mapping may be helpful and discusses techniques for CVS mapping and ablation.

Surgery for Ventricular Tachycardia.

The treatment of drug-refractory chronic ventricular tachycardia (VT) has undergone a revolution over the last 50 years. We now have automatic implantable cardioverter defibrillator therapy with pace-terminating capabilities, and catheter ablation of VT has refined mapping and improved methods of lesion generation. Between 1980 and 1993, Houston Methodist Hospital became a leader in the diagnosis and surgical ablation of VT and other arrhythmias. This is a brief account of that period and some of the experiences and lessons that have led to significant advances used today.

Postinfarct ventricular tachycardia substrate: Characterization and ablation of conduction channels using ripple mapping.

BACKGROUND: Conduction channels have been demonstrated within the postinfarct scar and seem to be co-located with the isthmus of ventricular tachycardia (VT). Mapping the local scar potentials (SPs) that define the conduction channels is often hindered by large far-field electrograms generated by healthy myocardium. OBJECTIVE: The purpose of this study was to map conduction channel using ripple mapping to categorize SPs temporally and anatomically. We tested the hypothesis that ablation of early SPs would eliminate the latest SPs without direct ablation. METHODS: Ripple maps of postinfarct scar were collected using the PentaRay (Biosense Webster) during normal rhythm. Maps were reviewed in reverse, and clusters of SPs were color-coded on the geometry, by timing, into early, intermediate, late, and terminal. Ablation was delivered sequentially from clusters of early SPs, checking for loss of terminal SPs as the endpoint. RESULTS: The protocol was performed in 11 patients. Mean mapping time was 65 ± 23 minutes, and a mean 3050 ± 1839 points was collected. SP timing ranged from 98.1 ± 60.5 ms to 214.8 ± 89.8 ms post QRS peak. Earliest SPs were present at the border, occupying 16.4% of scar, whereas latest SPs occupied 4.8% at the opposing border or core. Analysis took 15 ± 10 minutes to locate channels and identify ablation targets. It was possible to eliminate latest SPs in all patients without direct ablation (mean ablation time 16.3 ± 11.1 minutes). No VT recurrence was recorded (mean follow-up 10.1 ± 7.4 months). CONCLUSION: Conduction channels can be located using ripple mapping to analyze SPs. Ablation at channel entrances can eliminate the latest SPs and is associated with good medium-term results.

A novel Ventricular map of Electrograms DUration as a Method to identify areas of slow conduction for ventricular tachycardia ablation: The VEDUM pilot study.

BACKGROUND: Bipolar electrogram (EGM) duration is indicative of local activation property and, if prolonged, is useful to discover areas of slow conduction favoring arrhythmias. OBJECTIVE: The present study aimed to create a map of EGM duration during the ventricular tachycardia (VT) (Ventricular Electrograms DUration as a Method map [VEDUM map]) to verify if the slowest activation area is crucial for reentry and could represent a suitable target for rapid VT interruption during ablation. METHODS: Prospectively 30 patients were enrolled for this study. Twenty-one patients were selected, and 24 VT maps with complete circuit delineation (>90% tachycardia cycle length) were analyzed. Activation and VEDUM maps during VT as well as voltage maps during sinus rhythm were created. RESULTS: Twenty-two of 24 VTs (88%) were interrupted during the first radiofrequency delivery (mean time 7.3 ± 5.4 seconds; range 3-25 seconds) at the area with the longest EGM duration (212 ± 47 ms; range 113-330 ms). The mean percentage of the cycle length of VT covered by the EGM with the longest duration was 58% ± 12%. In 9 patients (37%), the longest EGM was located at the isthmus entrance, at the exit in 7 maps (30%), and the mid-isthmuses in 8 maps (33%). In 6 patients (25%), the EGM covered the full diastolic phase. The mean isthmus width was 28 ± 11 mm (range 16-48 mm; median 25 mm). CONCLUSION: A VEDUM map is highly accurate in defining a conductive vulnerable zone of the VT circuit. The longest EGM duration within the isthmus is highly predictive of rapid VT termination at the first radiofrequency delivery even in the case of large isthmuses.

Local abnormal ventricular activity detection in scar-related VT: Microelectrode versus conventional bipolar electrode.

BACKGROUND: Conventional bipolar electrodes (CBE) may be suboptimal to detect local abnormal ventricular activities (LAVAs). Microelectrodes (ME) may improve the detection of LAVAs. This study sought to elucidate the detectability of LAVAs using ME compared with CBE in patients with scar-related ventricular tachycardia (VT). METHODS: We included consecutive patients with structural heart disease who underwent radiofrequency catheter ablation for scar-related VT using either of the following catheters equipped with ME: QDOTTM or IntellaTip MIFITM. Detection field of LAVA potentials were classified as three types: Type 1 (both CBE and ME detected LAVA), Type 2 (CBE did not detect LAVA while ME did), and Type 3 (CBE detected LAVA while ME did not). RESULTS: In 16 patients (68 ± 16 years; 14 males), 260 LAVAs electrograms (QDOT = 72; MIFI = 188) were analyzed. Type 1, type 2, and type 3 detections were 70.8% (QDOT, 69.4%; MIFI, 71.3%), 20.0% (QDOT, 23.6%; MIFI, 18.6%) and 9.2% (QDOT, 6.9%; MIFI, 10.1%), respectively. The LAVAs amplitudes detected by ME were higher than those detected by CBE in both catheters (QDOT: ME 0.79 ± 0.50 mV vs. CBE 0.41 ± 0.42 mV, p = .001; MIFI: ME 0.73 ± 0.64 mV vs. CBE 0.38 ± 0.36 mV, p < .001). CONCLUSIONS: ME allow to identify 20% of LAVAs missed by CBE. ME showed higher amplitude LAVAs than CBE. However, 9.2% of LAVAs can still be missed by ME.

Electrophysiological and Pathological Impact of Medium-Dose External Carbon Ion and Proton Beam Radiation on the Left Ventricle in an Animal Model.

Background Medium-dose (25 gray) x-ray radiation therapy has recently been performed on patients with refractory ventricular tachyarrhythmias. Unlike x-ray, carbon ion and proton beam radiation can deliver most of their energy to the target tissues. This study investigated the electrophysiological and pathological changes caused by medium-dose carbon ion and proton beam radiation in the left ventricle (LV). Methods and Results External beam radiation in the whole LV was performed in 32 rabbits. A total of 9 rabbits were not irradiated (control). At the 3-month or 6-month follow-up, the animals underwent an open-chest electrophysiological study and were euthanized for histological analyses. No acute death occurred. Significant LV dysfunction was not seen. The surface ECG revealed a significant reduction in the P and QRS wave voltages in the radiation groups. The electrophysiological study showed that the local conduction times in each LV site were significantly longer and that the local LV bipolar voltages were significantly lower in the radiation groups than in the control rabbits. Histologically, apoptosis, fibrotic changes, and a decrease in the expression of the connexin 43 protein were seen in the LV myocardium. These changes were obvious at 3 months, and the effects were sustained 6 months after radiation. No histological changes were seen in the coronary artery and esophagus, but partial radiation pneumonitis was observed. Conclusions Medium-dose carbon ion and proton beam radiation in the whole LV resulted in a significant electrophysiological disturbance and pathological changes in the myocardium. Radiation of the arrhythmogenic substrate would modify the electrical status and potentially induce the antiarrhythmic effect.

Arrhythmic Risk Profile and Outcomes of Patients Undergoing Cardiac Sympathetic Denervation for Recurrent Monomorphic Ventricular Tachycardia After Ablation.

Background Cardiac sympathetic denervation (CSD) has been used as a bailout strategy for refractory ventricular tachycardia (VT). Risk of VT recurrence in patients with scar-related monomorphic VT referred for CSD and the extent to which CSD can modify this risk is unknown. We aimed to quantify arrhythmia recurrence risk and impact of CSD in this population. Methods and Results Adjusted competing risk time to event models were developed to adjust for risk of VT recurrence and sustained VT/implantable cardioverter-defibrillator shocks after VT ablation based on patient comorbidities at the time of VT ablation. Adjusted VT and implantable cardioverter-defibrillator shock recurrence rates were estimated for the subgroup who subsequently required CSD after ablation. The expected adjusted recurrence rates were then compared with the observed rates after CSD. Data from 381 patients with scar-mediated monomorphic VT who underwent VT ablation were analyzed, excluding patients with polymorphic VT. Sixty eight patients underwent CSD for recurrent VT. CSD reduced the expected adjusted VT recurrence rate by 36% (expected rate of 5.61 versus observed rate of 3.58 per 100 person-months, P=0.01) and the sustained VT/implantable cardioverter-defibrillator shock rates by 34% (expected rate of 4.34 versus observed 2.85 per 100 person-months, P=0.03). The median number of sustained VT/implantable cardioverter-defibrillator shocks in the year before versus the year after CSD was reduced by 90% (10 versus 1, P<0.0001). Conclusions Patients referred for CSD for refractory scar-mediated monomorphic VT are at a higher risk of VT recurrence after ablation as compared with those not requiring CSD, mostly because of their cardiac comorbidities. CSD significantly reduced both the expected risk of recurrences and VT burden.

Machine Learned Cellular Phenotypes in Cardiomyopathy Predict Sudden Death.

RATIONALE: Susceptibility to VT/VF (ventricular tachycardia/fibrillation) is difficult to predict in patients with ischemic cardiomyopathy either by clinical tools or by attempting to translate cellular mechanisms to the bedside. OBJECTIVE: To develop computational phenotypes of patients with ischemic cardiomyopathy, by training then interpreting machine learning of ventricular monophasic action potentials (MAPs) to reveal phenotypes that predict long-term outcomes. METHODS AND RESULTS: We recorded 5706 ventricular MAPs in 42 patients with coronary artery disease and left ventricular ejection fraction ≤40% during steady-state pacing. Patients were randomly allocated to independent training and testing cohorts in a 70:30 ratio, repeated K=10-fold. Support vector machines and convolutional neural networks were trained to 2 end points: (1) sustained VT/VF or (2) mortality at 3 years. Support vector machines provided superior classification. For patient-level predictions, we computed personalized MAP scores as the proportion of MAP beats predicting each end point. Patient-level predictions in independent test cohorts yielded c-statistics of 0.90 for sustained VT/VF (95% CI, 0.76-1.00) and 0.91 for mortality (95% CI, 0.83-1.00) and were the most significant multivariate predictors. Interpreting trained support vector machine revealed MAP morphologies that, using in silico modeling, revealed higher L-type calcium current or sodium-calcium exchanger as predominant phenotypes for VT/VF. CONCLUSIONS: Machine learning of action potential recordings in patients revealed novel phenotypes for long-term outcomes in ischemic cardiomyopathy. Such computational phenotypes provide an approach which may reveal cellular mechanisms for clinical outcomes and could be applied to other conditions.

Close-coupled pacing to identify the "functional" substrate of ventricular tachycardia: Long-term outcomes of the paced electrogram feature analysis technique.

BACKGROUND: The conduction delay and block that compose the critical isthmus of macroreentrant ventricular tachycardia (VT) is partly "functional" in that they only occur at faster cycle lengths. Close-coupled pacing stresses the myocardium's conduction capacity and may reveal late potentials (LPs) and fractionation. Interest has emerged in targeting this functional substrate. OBJECTIVE: The purpose of this study was to assess the feasibility and efficacy of a functional substrate VT ablation strategy. METHODS: Patients with scar-related VT undergoing their first ablation were recruited. A closely coupled extrastimulus (ventricular effective refractory period + 30 ms) was delivered at the right ventricular apex while mapping with a high-density catheter. Sites of functional impaired conduction exhibited increased electrogram duration due to LPs/fractionation. The time to last deflection was annotated on an electroanatomic map, readily identifying ablation targets. RESULTS: A total of 40 patients were recruited (34 [85%] ischemic). Median procedure duration was 330 minutes (interquartile range [IQR] 300-369), and ablation time was 49.4 minutes (IQR 33.8-48.3). Median functional substrate area was 41.9 cm2 (IQR 22.1-73.9). It was similarly distributed across bipolar voltage zones. Noninducibility was achieved in 34 of 40 patients (85%). Median follow-up was 711 days (IQR 255.5-972.8), during which 35 of 39 patients (89.7%) did not have VT recurrence, and 3 of 39 (7.5%) died. Antiarrhythmic drugs were continued in 53.8% (21/39). CONCLUSION: Functional substrate ablation resulted in high rates of noninducibility and freedom from VT. Mapping times were increased considerably. Our findings add to the encouraging trend reported by related techniques. Randomized multicenter trials are warranted to assess this next phase of VT ablation.