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.

Cardiac sympathetic activation circumvents high-dose beta blocker therapy in part through release of neuropeptide Y.

The sympathetic nervous system plays an important role in the occurrence of ventricular tachycardia (VT). Many patients, however, experience VT despite maximal doses of beta blocker therapy, possibly due to the effects of sympathetic cotransmitters such as neuropeptide Y (NPY). The purpose of this study was to determine, in a porcine model, whether propranolol at doses higher than clinically recommended could block ventricular electrophysiological effects of sympathoexcitation via stellate ganglia stimulation, and if any residual effects are mediated by NPY. Greater release of cardiac NPY was observed at higher sympathetic stimulation frequencies (10 and 20 vs. 4 Hz). Despite treatment with even higher doses of propranolol (1.0 mg/kg), electrophysiological effects of sympathetic stimulation remained, with residual shortening of activation recovery interval (ARI), a surrogate of action potential duration (APD). Adjuvant treatment with the NPY Y1 receptor antagonist BIBO 3304, however, reduced these electrophysiological effects while augmenting inotropy. These data demonstrate that high-dose beta blocker therapy is insufficient to block electrophysiological effects of sympathoexcitation, and a portion of these electrical effects in vivo are mediated by NPY. Y1 receptor blockade may represent a promising adjuvant therapy to beta-adrenergic receptor blockade.

Three-dimensional myocardial scar characterization from the endocardium: Usefulness of endocardial unipolar electroanatomic mapping.

Epicardial ablation may be required to eliminate ventricular tachycardia (VT) in patients with underlying structural heart disease. The decision to gain epicardial access is frequently based on the suspicion of an epicardial origin for the VT and/or presence of an arrhythmogenic substrate. Epicardial pathology and VT is frequently present in patients with nonischemic right and/or left cardiomyopathies even in the setting of modest or no endocardial bipolar voltage substrate. In this setting, unipolar voltage mapping from the endocardium serves to help identify midmyocardial and/or epicardial VT substrate. The additional value of endocardial unipolar mapping includes its usefulness to predict the clinical outcome after VT ablation, to determine the irreversibility of myocardial disease, and to guide endomyocardial biopsy procedures to specific areas of intramural scarring. In this review, we aim to provide a guide to the use of endocardial unipolar mapping and its appropriate interpretation in a variety of clinical situations.

Feasibility of Performing Radiofrequency Catheter Ablation and Endomyocardial Biopsy in the Same Setting.

In patients with unexplained cardiomyopathy, electroanatomical mapping can identify abnormal tissue to target during electrophysiology-guided endomyocardial biopsy (EP-guided EMB). The objective of this study is to determine whether catheter ablation performed in the same setting as EP-guided EMB increases procedural risk. Sixty-seven patients (mean age 54.4 ± 13.8, 57% male) undergoing EP-guided EMB were included. Radiofrequency catheter ablation was performed in 17 patients (25%) for ventricular arrhythmias and in 2 (3%) for typical atrial flutter. Femoral arterial access was obtained in 90% ablation patients and 40% biopsy-only patients; vascular access complications were more common in the ablation group than in the EMB-only group (p = 0.02). There were no significant differences in rate of tricuspid regurgitation, thromboembolism, or pericardial effusion, whether procedural anticoagulation was used. In conclusion, catheter ablation and procedural anticoagulation can be combined with EP-guided EMB with an increased risk of vascular access complications, but no significant increase in intracardiac complications.

EL20, a potent antiarrhythmic compound, selectively inhibits calmodulin-deficient ryanodine receptor type 2.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disorder caused by mutations in the cardiac ryanodine receptor RyR2 that increase diastolic calcium cation (Ca2+) leak from the sarcoplasmic reticulum (SR). Calmodulin (CaM) dissociation from RyR2 has been associated with diastolic Ca2+ leak in heart failure. OBJECTIVE: Determine whether the tetracaine-derivative compound EL20 inhibits abnormal Ca2+ release from RyR2 in a CPVT model and investigate the underlying mechanism of inhibition. METHODS: Spontaneous Ca2+ sparks in cardiomyocytes and inducible ventricular tachycardia were assessed in a CPVT mouse model, which is heterozygous for the R176Q mutation in RyR2 (R176Q/+ mice) in the presence of EL20 or vehicle. Single-channel studies using sheep cardiac SR or purified RyR2 reconstituted into proteoliposomes with and without exogenous CaM were used to assess mechanisms of inhibition. RESULTS: EL20 potently inhibits abnormal Ca2+ release in R176Q/+ myocytes (half-maximal inhibitory concentration = 35.4 nM) and diminishes arrhythmia in R176Q/+ mice. EL20 inhibition of single-channel activity of purified RyR2 occurs in a similar range as seen in R176Q/+ myocytes (half-maximal inhibitory concentration = 8.2 nM). Inhibition of single-channel activity for cardiac SR or purified RyR2 supplemented with 100-nM or 1-µM CaM shows a 200- to 1000-fold reduction in potency. CONCLUSION: This work provides a potential therapeutic mechanism for the development of antiarrhythmic compounds that inhibit leaky RyR2 resulting from CaM dissociation, which is often associated with failing hearts. Our data also suggest that CaM dissociation may contribute to the pathogenesis of arrhythmias with the CPVT-linked R176Q mutation.

Effects of hawthorn ( Crataegus pentagyna) leaf extract on electrophysiologic properties of cardiomyocytes derived from human cardiac arrhythmia-specific induced pluripotent stem cells.

Cardiac arrhythmias are major life-threatening conditions. The landmark discovery of induced pluripotent stem cells has provided a promising in vitro system for modeling hereditary cardiac arrhythmias as well as drug development and toxicity testing. Nowadays, nutraceuticals are frequently used as supplements for cardiovascular therapy. Here we studied the cardiac effects of hawthorn ( Crataegus pentagyna) leaf extract using cardiomyocytes (CMs) differentiated from healthy human embryonic stem cells, long QT syndrome type 2 (LQTS2), and catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) patient-specific induced pluripotent stem cells. The hydroalcoholic extract resulted in a dose-dependent negative chronotropic effect in all CM preparations leading to a significant reduction at 1000 µg/ml. This was accompanied by prolongation of field potential durations, although with different magnitudes in CMs from different human embryonic stem cell and iPSC lines. Hawthorn further prolonged field potential durations in LQTS2 CMs but reduced the beating frequencies and occurrence of immature field potentials triggered by ß1-adrenergic stimulation in CPVT1 CMs at 300 and 1000 µg/ml. Furthermore, isoquercetin and vitexin flavonoids significantly slowed down isoproterenol (5 µM)-induced beating frequencies at 3 and 10 µg/ml. Therefore, C. pentagyna leaf extract and its isoquercetin and vitexin flavonoids may be introduced as a novel nutraceutical with antiarrhythmic potential for CPVT1 patients.-Pahlavan, S., Tousi, M. S., Ayyari, M., Alirezalu, A., Ansari, H., Saric, T., Baharvand, H. Effects of hawthorn ( Crataegus pentagyna) leaf extract on electrophysiologic properties of cardiomyocytes derived from human cardiac arrhythmia-specific induced pluripotent stem cells.

Cardiac magnetic resonance-aided scar dechanneling: Influence on acute and long-term outcomes.

BACKGROUND: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) provides tissue characterization of ventricular myocardium and scar that can be depicted as pixel signal intensity (PSI) maps. OBJECTIVE: To assess the possible benefit of guiding the ventricular tachycardia (VT) substrate mapping by integrating these PSI maps into the navigation system. METHODS: In total, 159 consecutive patients (66 ± 11 years old, 151 men [95%]) with scar-related left ventricular (LV) VT were included. VT substrate ablation used the scar dechanneling technique. A CMR-aided ablation using the PSI maps was performed in 54 patients (34%). Procedural data as well as acute and long-term outcomes were compared with those of the remaining 105 patients (66%). RESULTS: Mean procedure duration and fluoroscopy time were 229 ± 67 minutes and 20 ± 9 minutes, respectively, without significant differences between groups. Both the number of radiofrequency (RF) applications and RF delivery time were lower in the CMR-aided group (28 ± 18 applications vs 36 ± 18 applications, P = .037, and 19 ± 12 minutes vs 27 ± 16 minutes, P = .009, respectively). After substrate ablation, monomorphic VT inducibility was lower in the CMR-aided than in the control group (17 [32%] vs 53 [51%] patients, P = .022). After a mean follow-up period of 20 ± 19 months, patients from the CMR-aided group had a lower recurrence rate than those in the control group (10 patients [18.5%] vs 46 patients [43.8%], respectively, P = .002; log-rank P = .017). Multivariate analysis found that CMR-aided ablation (hazard ratio, 0.48 [95% Confirdence Interval (CI) 0.24-0.96], P = .037) was an independent predictor of recurrences. CONCLUSION: CMR-aided scar dechanneling is associated with a lower need for RF delivery, higher noninducibility rates after substrate ablation, and a higher VT-recurrence-free survival.

Myocardial wall thinning predicts transmural substrate in patients with scar-related ventricular tachycardia.

BACKGROUND: Scar-related ventricular tachycardia (VT) arises from specific substrate according to etiology. OBJECTIVE: The purpose of this study was to evaluate the relationship between wall thinning (WT) on multidetector computed tomography (MDCT) and local abnormal ventricular activity (LAVA) in patients with ischemic cardiomyopathy (ICM), postmyocarditis (PMC), and dilated cardiomyopathy (DCM). METHODS: Forty-two patients (40 male, age 58 ± 13 years, 22 ICM, 11 PMC, 9 DCM) underwent MDCT before a combined endo-/epicardial VT ablation procedure. WT (<5 mm) and severe wall thinning (SWT) (<2 mm) area on MDCT were compared to the prevalence of endo-/epicardial LAVA during sinus rhythm. RESULTS: WT and SWT were found on MDCT in 36 (86%) and 20 (48%) with 42 ± 37 cm2 and 26 ± 24 cm2, respectively. SWT was frequently detected in ICM (ICM 77% vs PMC 27% vs DCM 0%, P <.001). LAVA were frequently observed on the endocardium in ICM and on the epicardium in PMC. Endo-/epicardial facing LAVA were frequently found within SWT areas (91% in <2 mm, 9% in 2-5 mm, and 0% in >5 mm, P < .001). In SWT areas, the presence of endocardial LAVA in ICM and epicardial LAVA in PMC predicted opposite facing LAVA with sensitivity and specificity of 78% and 48% and 79% and 98%, respectively. SWT predicted epicardial LAVA in ICM and endocardial LAVA in PMC with sensitivity and specificity of 89% and 100%, and 100% and 100%, respectively. CONCLUSION: SWT is frequently found in ICM and PMC but is not common in DCM. SWT predicts LAVA on the opposite side of the wall (epicardial in ICM and endocardial in PMC), indicating transmural VT substrate. MDCT is useful for identifying VT substrate and helpful for understanding the mechanisms of the location of VT substrate domain.

A Prospective Study of Ripple Mapping the Post-Infarct Ventricular Scar to Guide Substrate Ablation for Ventricular Tachycardia.

BACKGROUND: Post-infarct ventricular tachycardia is associated with channels of surviving myocardium within scar characterized by fractionated and low-amplitude signals usually occurring late during sinus rhythm. Conventional automated algorithms for 3-dimensional electro-anatomic mapping cannot differentiate the delayed local signal of conduction within the scar from the initial far-field signal generated by surrounding healthy tissue. Ripple mapping displays every deflection of an electrogram, thereby providing fully informative activation sequences. We prospectively used CARTO-based ripple maps to identify conducting channels as a target for ablation. METHODS AND RESULTS: High-density bipolar left ventricular endocardial electrograms were collected using CARTO3v4 in sinus rhythm or ventricular pacing and reviewed for ripple mapping conducting channel identification. Fifteen consecutive patients (median age 68 years, left ventricular ejection fraction 30%) were studied (6 month preprocedural implantable cardioverter defibrillator therapies: median 19 ATP events [Q1-Q3=4-93] and 1 shock [Q1-Q3=0-3]). Scar (<1.5 mV) occupied a median 29% of the total surface area (median 540 points collected within scar). A median of 2 ripple mapping conducting channels were seen within each scar (length 60 mm; initial component 0.44 mV; delayed component 0.20 mV; conduction 55 cm/s). Ablation was performed along all identified ripple mapping conducting channels (median 18 lesions) and any presumed interconnected late-activating sites (median 6 lesions; Q1-Q3=2-12). The diastolic isthmus in ventricular tachycardia was mapped in 3 patients and colocated within the ripple mapping conducting channels identified. Ventricular tachycardia was noninducible in 85% of patients post ablation, and 71% remain free of ventricular tachycardia recurrence at 6-month median follow-up. CONCLUSIONS: Ripple mapping can be used to identify conduction channels within scar to guide functional substrate ablation.

Pathological autopsy of a patient that underwent a successful ablation of an electrical storm from the left ventricular summit.

A 65-year-old man with non-ischemic cardiomyopathy, underwent an autopsy 2 months after the successful ablation of a sustained left ventricular (LV) summit ventricular tachycardia (VT). The patient died due to interstitial pneumonia from amiodarone use. The earliest activation sites of the VT were documented from both inside the anterior interventricular vein (AIV) and epicardial surface. The diameter of the AIV was 3-4 mm, and the radiofrequency (RF) lesion inside the AIV was a slight lesion due to high impedance with a high temperature. The lesion from the epicardial surface was also superficial and insufficient due to neighboring coronary arteries and the existence of epicardial fat. A successful application was performed from the LV endocardium, and diffuse myocardial fibrosis was observed in the mid-myocardium including inside the RF lesions. The actual relationship between the myocardial fibrosis and LV summit VT remains unclear, but this case showed the difficulty of achieving a successful ablation from the epicardial side, when the focus exists in the mid-myocardium around the LV summit.

A swine model of infarct-related reentrant ventricular tachycardia: Electroanatomic, magnetic resonance, and histopathological characterization.

BACKGROUND: Human ventricular tachycardia (VT) after myocardial infarction usually occurs because of subendocardial reentrant circuits originating in scar tissue that borders surviving myocardial bundles. Several preclinical large animal models have been used to further study postinfarct reentrant VT, but with varied experimental methodologies and limited evaluation of the underlying substrate or induced arrhythmia mechanism. OBJECTIVE: We aimed to develop and characterize a swine model of scar-related reentrant VT. METHODS: Thirty-five Yorkshire swine underwent 180-minute occlusion of the left anterior descending coronary artery. Thirty-one animals (89%) survived the 6-8-week survival period. These animals underwent cardiac magnetic resonance imaging followed by electrophysiology study, detailed electroanatomic mapping, and histopathological analysis. RESULTS: Left ventricular (LV) ejection fraction measured using CMR imaging was 36% ± 6.6% with anteroseptal wall motion abnormality and late gadolinium enhancement across 12.5% ± 4.1% of the LV surface area. Low voltage measured using endocardial electroanatomic mapping encompassed 11.1% ± 3.5% of the LV surface area (bipolar voltage ≤1.5 mV) with anterior, anteroseptal, and anterolateral involvement. Reentrant circuits mapped were largely determined by functional rather than fix anatomical barriers, consistent with "pseudo-block" due to anisotropic conduction. Sustained monomorphic VT was induced in 28 of 31 swine (90%) (67 VTs; 2.4 ± 1.1; range 1-4) and characterized as reentry. VT circuits were subendocardial, with an arrhythmogenic substrate characterized by transmural anterior scar with varying degrees of fibrosis and myocardial fiber disarray on the septal and lateral borders. CONCLUSION: This is a well-characterized swine model of scar-related subendocardial reentrant VT. This model can serve as the basis for further investigation in the physiology and therapeutics of humanlike postinfarction reentrant VT.

Single- and dual-site pace mapping of idiopathic septal intramural ventricular arrhythmias.

BACKGROUND: Pace mapping (PM) is used to identify the origin of ventricular arrhythmias (VAs). For intramural VAs, the site of origin often cannot be reached and therefore PM is less accurate. OBJECTIVE: The purpose of this study was to assess the value of single- and dual-site pace maps to differentiate intramural from nonintramural VAs. METHODS: In 18 consecutive patients with idiopathic intramural VAs, pace mapping was performed at 2 breakthrough sites in adjacent anatomic structures. Twelve-lead electrocardiograms of the 2 pace maps were averaged in MATLAB and compared (correlation coefficient [CC]) with the targeted VA. Dual-site pace mapping was performed in a control group of 18 patients with nonintramural VAs at the sites of earliest electrical activation and a breakthrough site in an adjacent anatomic location. RESULTS: Dual-site pace maps had a higher CC than did best single-site pace maps (0.87 ± 0.1 vs 0.81 ± 0.16; P = .02) in patients with intramural VAs. At the site of origin, single-site pace maps had a higher CC than did dual-site pace maps obtained from adjacent anatomic locations (0.93 ± 0.04 vs 0.89 ± 0.05; P = .0004) in patients with nonintramural VAs. Sensitivity, specificity, positive predictive value, and negative predictive value of dual-site pace maps for identifying an intramural VA were 89%, 82%, 84%, 88%, and 86%, respectively. Furthermore, the receiver operating characteristic curve analysis revealed that a CC cutoff value of ≤0.86 for a single-site pace map best differentiated intramural from nonintramural VAs. CONCLUSION: A higher CC value for a dual-site pace map obtained from the earliest breakthrough site as well as a CC cutoff value of ≤0.86 for a single-site pace map obtained from the site of earliest electrical activation can best differentiate intramural from nonintramural VAs.

Substrate mapping for unstable ventricular tachycardia.

The primary goal of catheter ablation of scar-related ventricular tachycardia (VT) is the interruption of critical areas of slow conduction responsible for the development and maintenance of the reentrant VT circuit. Most patients with scar-related VT present with unstable arrhythmias that are not amenable to interrogation from multiple sites to define the VT circuit based on the intracardiac activation sequence and the response to entrainment mapping. In order to effectively target unstable VTs, a number of ablation approaches have been described with the aim of targeting the abnormal substrate defined with mapping in sinus or paced rhythm. Some of these strategies (eg, late potential and local abnormal ventricular activity ablation or scar homogenization) target the entire abnormal substrate harboring abnormal electrograms, defined with a variety of different criteria. Scar dechanneling, linear ablation through sites matching VT with pacing, and the core isolation approach focus on more discrete regions within the abnormal substrate that have been proven relevant to the clinical and/or inducible arrhythmias by means of physiologic maneuvers, although this does not necessarily translate to fewer radiofrequency lesions to achieve the procedural end-point. Observational studies evaluating different substrate-based ablation techniques have reported fairly uniform arrhythmia-free survivals at short- and mid-term follow-up, although direct comparisons between different techniques are lacking. In this article, we summarize the different state-of-the-art substrate mapping and ablation approaches for targeting unstable VT, with a particular focus on the relative merits and limitations of the described techniques.

Value of Cardiac Magnetic Resonance Imaging in Patients With Failed Ablation Procedures for Ventricular Tachycardia.

BACKGROUND: Ventricular tachycardia (VT) in patients with cardiomyopathy originates in scar tissue. Intramural or epicardial scar may result in ineffective ablation if mapping and ablation are limited to the endocardium. The purpose of this study was to investigate whether preprocedural magnetic resonance imaging (MRI) is beneficial in patients with failed endocardial VT ablations in determining an appropriate ablation strategy. METHODS AND RESULTS: A cardiac MRI was performed in 20 patients with a failed ablation procedure and cardiomyopathy (nonischemic n = 12, ischemic n = 8). A subsequent ablation strategy was determined by a delayed enhanced MRI (DE-MRI) and an epicardial subxyphoid access was planned only in patients with epicardial or intramural free-wall scar. MRIs were performed in all patients with or without an implanted cardioverter defibrillator (ICD). The location of scar tissue in the MRI predicted the origin of VT in all patients. In 9/20 patients an epicardial procedure was performed based on the result of the MRI. An endocardial procedure was performed in the remaining 11 patients who had either endocardial or septal scarring and one patient in whom the MRI only showed artifact. Five patients remained inducible postablation and four patients had VT recurrence within a follow-up period of 17 ± 22 months. All of the latter patients had an intramural scar pattern. CONCLUSIONS: Imaging with DE-MRI prior to VT ablation in patients with previously failed endocardial ablation procedures is beneficial in identifying an ablation strategy, helps to focus on an area of interest intraprocedurally, and provides valuable outcomes information.

Irrigated Needle Ablation Creates Larger and More Transmural Ventricular Lesions Compared With Standard Unipolar Ablation in an Ovine Model.

BACKGROUND: Ventricular tachycardia recurrence can occur after ventricular tachycardia ablation because of incomplete and nontransmural ventricular lesion formation. We sought to compare the lesions made by a novel irrigated needle catheter to conventional radiofrequency lesions. METHODS AND RESULTS: Thirteen female sheep (4.6±0.7 years, 54±8 kg) were studied. In 7 sheep, 60-s radiofrequency applications were performed using an irrigated needle catheter. In 6 sheep, conventional lesions were made using a 4-mm irrigated catheter. 1.5T in vivo and high-density magnetic resonance imaging (9.4T) were performed on explanted hearts from animals receiving needle radiofrequency. Conventional lesion volume was calculated as (1/6)×π×(A×B(2)+C×D(2)/2). Needle lesion volume was measured as Σ(π×r(2))/2 with a slice thickness of 1 mm. The dimensions of all lesions were also measured on gross pathology. Additional histological analysis of the needle lesions was performed. One hundred twenty endocardial left ventricular ablation lesions (conventional, n=60; needle, n=60) were created. At necropsy, more lesions were found using needle versus conventional radiofrequency (90% versus 75%; P<0.05). Comparing needle versus conventional radiofrequency: lesion volume was larger (1030±362 versus 488±384 mm(3); P<0.001), lesion depth was increased (9.9±2.7 versus 5±2.4 mm; P<0.001), and more transmural lesions were created (62.5% versus 17%; P<0.01). Pericardial contrast injection was observed in 4 apical attempts using needle radiofrequency, however, with no adverse effects. Steam pops occurred in 3 attempts using conventional radiofrequency. CONCLUSIONS: Irrigated needle ablation is associated with more frequent, larger, deeper, and more often transmural lesions compared with conventional irrigated ablation. This technology might be of value to treat intramural or epicardial ventricular tachycardia substrates resistant to conventional ablation.

Finding the rhythm of sudden cardiac death: new opportunities using induced pluripotent stem cell-derived cardiomyocytes.

Sudden cardiac death is a common cause of death in patients with structural heart disease, genetic mutations, or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with sudden cardiac death. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology, including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single-ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell-derived cardiomyocytes resemble, but are not identical, adult human cardiomyocytes and provide a new platform for studying arrhythmic disorders leading to sudden cardiac death. A variety of platforms exist to phenotype cellular models, including conventional and automated patch clamp, multielectrode array, and computational modeling. Induced pluripotent stem cell-derived cardiomyocytes have been used to study long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and other hereditary cardiac disorders. Although induced pluripotent stem cell-derived cardiomyocytes are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of sudden cardiac death.

Impact of earliest activation site location in the septal right ventricular outflow tract for identification of left vs right outflow tract origin of idiopathic ventricular arrhythmias.

BACKGROUND: The earliest activation site (EAS) location in the septal right ventricular outflow tract (RVOT) could be an additional mapping data predictor of left ventricular outflow tract (LVOT) vs RVOT origin of idiopathic ventricular arrhythmias (VAs). OBJECTIVE: The purpose of this study was to assess the impact of EAS location in predicting LVOT vs RVOT origin. METHODS: Macroscopic and histologic study was performed in 12 postmortem hearts. Electroanatomic maps (EAMs) from 37 patients with outflow tract (OT) VA with the EAS in the septal RVOT were analyzed. Pulmonary valve (PV) was defined by voltage scanning after validation of voltage thresholds by image integration. EAM measurements were correlated with those of macroscopic/histologic study. RESULTS: A cutoff value of 1.9 mV discriminated between subvalvular and supravalvular positions (90% sensitivity, 96% specificity). EAS ≥1 cm below PV excluded RVOT site of origin (SOO). According to anatomic findings (distance PV-left coronary cusp = 5 ± 3 vs PV-right coronary cusp = 11 ± 5 mm), EAS-PV distance was significantly shorter in VAs arising from left coronary cusp than from the other LVOT locations (4.2 ± 5.4 mm vs 9.2 ± 7 mm; P = .034). The 10-ms isochronal longitudinal/perpendicular diameter ratio was higher in the RVOT vs the LVOT SOO group (1.97 ± 1.2 vs 0.79 ± 0.49; P = .001). An algorithm based on EAS-PV distance and the 10-ms isochronal longitudinal/perpendicular diameter ratio predicted LVOT SOO with 91% sensitivity and 100% specificity. CONCLUSION: An algorithm based on the EAS-PV distance and the 10-ms isochronal longitudinal/perpendicular diameter ratio accurately predicts LVOT vs RVOT SOO in outflow tract VAs with EAS in the septal RVOT.

CMR-based identification of critical isthmus sites of ischemic and nonischemic ventricular tachycardia.

OBJECTIVES: This study evaluates whether contrast-enhanced (CE) cardiac magnetic resonance (CMR) can be used to identify critical isthmus sites for ventricular tachycardia (VT) in ischemic and nonischemic heart disease. BACKGROUND: Fibrosis interspersed with viable myocytes may cause re-entrant VT. CE-CMR has the ability to accurately delineate fibrosis. METHODS: Patients who underwent VT ablation with CE-CMR integration were included. After the procedure, critical isthmus sites (defined as sites with a ≥11 of 12 pacemap, concealed entrainment, or VT termination during ablation) were projected on CMR-derived 3-dimensional (3D) scar reconstructions. The scar transmurality and signal intensity at all critical isthmus, central isthmus, and exit sites were compared to the average of the entire scar. The distance to >75% transmural scar and to the core-border zone (BZ) transition was calculated. The area within 5 mm of both >75% transmural scar and the core-BZ transition was calculated. RESULTS: In 44 patients (23 ischemic and 21 nonischemic, left ventricular ejection fraction 44 ± 12%), a total of 110 VTs were induced (cycle length 290 ± 67 ms). Critical isthmus sites were identified for 78 VTs (71%) based on ≥11 of 12 pacemaps (67 VTs), concealed entrainment (10 VTs), and/or termination (30 VTs). The critical isthmus sites, and in particular central isthmus sites, had high scar transmurality and signal intensity compared with the average of the entire scar. Of the pacemap, concealed entrainment, and termination sites, 74%, 100%, and 84% were within 5 mm of >75% transmural scar, and 67%, 100%, and 94% were within 5 mm of the core-BZ transition, respectively. The areas within 5 mm of both >75% transmural scar and the core-BZ transition (median 13% of LV) contained all concealed entrainment sites and 77% of termination sites. CONCLUSIONS: Both in ischemic and nonischemic VT, critical isthmus sites are typically located in close proximity to the CMR-derived core-BZ transition and to >75% transmural scar. These findings suggest that CMR-derived scar characteristics may guide to critical isthmus sites during VT ablation.

Variations of electroanatomic substrates and markers of successful ablation in idiopathic left ventricular tachycardia: role of electroanatomic substrates and potential mechanism of tachycardia.

OBJECTIVES: The variation of the substrates of verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) was not understood. The purpose of this study was to investigate the variation of electroanatomic substrate [slow conduction zone (SCZ) and left ventricular conduction system (LVCS)] in ILVT and control individuals and markers of successful ablation. METHODS: Electroanatomical mapping was performed during sinus rhythm in 20 ILVT patients and 26 control individuals with paroxysmal supraventricular tachycardia. LVCS and SCZ were tagged in geometry and the anatomic aspects were investigated. RESULTS: According to the distribution of Purkinje potential, LVCS was distinguished into three types: left bundle branch (LBB) was divided into two discrete fascicles without interconnections; divided into three separate fascicles; and fanlike structure distribution over septum broadly. The length of LBB and its fascicles in patients with ILVT were slightly longer than those of controls (P > 0.05). In the ILVT group, the SCZ was located at the inferoposterior septum in 17, inferior apical septum in one and two SCZs were located at the posterior and mid-septal in the other two patients, which were greater in size and longer in length than those of six controls (P < 0.05). At the crossover junction area with diastolic potential and Purkinje potential, with the size of 1.5 ± 0.4 cm(2), concealed entertainment and ablation were obtained successfully in all patients with ILVT. CONCLUSION: The anatomy of the LVCS and SCZ is highly variable in patients with ILVT, and the crossover junction area with diastolic potential and Purkinje potential might be a marker of ablation.