An approach to help differentiate postinfarct scar from borderzone tissue using Ripple Mapping during ventricular tachycardia ablation.

BACKGROUND: Ventricular scar is traditionally highlighted on a bipolar voltage (BiVolt) map in areas of myocardium <0.50 mV. We describe an alternative approach using Ripple Mapping (RM) superimposed onto a BiVolt map to differentiate postinfarct scar from conducting borderzone (BZ) during ventricular tachycardia (VT) ablation. METHODS: Fifteen consecutive patients (left ventricular ejection fraction 30 ± 7%) underwent endocardial left ventricle pentaray mapping (median 5148 points) and ablation targeting areas of late Ripple activation. BiVolt maps were studied offline at initial voltage of 0.50-0.50 mV to binarize the color display (red and purple). RMs were superimposed, and the BiVolt limits were sequentially reduced until only areas devoid of Ripple bars appeared red, defined as RM-scar. The surrounding area supporting conducting Ripple wavefronts in tissue <0.50 mV defined the RM-BZ. RESULTS: RM-scar was significantly smaller than the traditional 0.50 mV cutoff (median 4% vs. 12% shell area, p < .001). 65 ± 16% of tissue <0.50 mV supported Ripple activation within the RM-BZ. The mean BiVolt threshold that differentiated RM-scar from BZ tissue was 0.22 ± 0.07 mV, though this ranged widely (from 0.12 to 0.35 mV). In this study, septal infarcts (7/15) were associated with more rapid VTs (282 vs. 347 ms, p = .001), and had a greater proportion of RM-BZ to RM-scar (median ratio 3.2 vs. 1.2, p = .013) with faster RM-BZ conduction speed (0.72 vs. 0.34 m/s, p = .001). Conversely, scars that supported hemodynamically stable sustained VT (6/15) were slower (367 ± 38 ms), had a smaller proportion of RM-BZ to RM-scar (median ratio 1.2 vs. 3.2, p = .059), and slower RM-BZ conduction speed (0.36 vs. 0.63 m/s, p = .036). RM guided ablation collocated within 66 ± 20% of RM-BZ, most concentrated around the RM-scar perimeter, with significant VT reduction (median 4.0 episodes preablation vs. 0 post, p < .001) at 11 ± 6 months follow-up. CONCLUSION: Postinfarct scars appear significantly smaller than traditional 0.50 mV cut-offs suggest, with voltage thresholds unique to each patient.

Retrograde aortic access during ventricular tachycardia ablation: Indications, techniques, and challenges.

The retrograde aortic (RA) route is a widely used access route for mapping and ablation of ventricular tachycardias (VT) arising from the left ventricular endocardium. With the expanding role of VT ablation in patients with significant comorbidity, the choice between the RA and transseptal access routes is an increasingly important consideration. An individualized decision based on the location of the arrhythmogenic substrate, vascular anatomy, aortic valve morphology, and operator experience is necessary when deciding on the optimal access route. Among patients with challenging vascular anatomy, growing experience from structural interventions such as transcatheter aortic valve replacements and peripheral vascular interventions has provided valuable insights into techniques for safe retrograde access. The present review focuses on patient selection for RA access, potential complications associated with the technique, and optimal approaches for access in patients with challenging vascular or aortic valve anatomy.

Right ventricular scar-related ventricular tachycardia in nonischemic cardiomyopathy: Electrophysiological characteristics, mapping, and ablation of underlying heart disease.

BACKGROUND: Right ventricular (RV)-scar related ventricular tachycardia (VT) is often due to arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) or cardiac sarcoidosis (CS), but some patients whose clinical course has not been described do not fulfill diagnostic criteria for these diseases. We sought to characterize the electrophysiologic substrate and catheter ablation outcomes of such patients, termed RV cardiomyopathy of unknown source (RCUS). METHODS AND RESULTS: Data of 100 consecutive patients who presented with RV cardiomyopathy and/or RV-related VT for ablation were reviewed (51 ARVC/D, 22 CS; 27 RCUS). Compared to ARVC/D, RCUS patients were older (P = 0.001), less commonly had RV dilatation (P = 0.001) or dysfunction (P = 0.01) and fragmented QRS, parietal block, and T-wave inversion. Compared to CS, R-CUS patients had less severe LV dysfunction. Extent and distribution of endocardial/epicardial scar and inducible VTs in RCUS patients were comparable with ARVC/D and CS patients. At a median follow-up of 23 months, RCUS patients had more favorable VT-free survival (RCUS 71%, ARVC/D 60%, CS 41%, P = 0.03) and survival free of death or cardiac transplant (RCUS 92%, ARVC/D 92%, CS 62%, P = 0.01). No RCUS patients developed new criteria for ARVC/D or CS in follow-up. CONCLUSIONS: Up to one-third of patients with RV scar-related VT are not classifiable as ARVC/D or CS. These patients had a somewhat better prognosis than ARVC/D or sarcoid and did not develop evidence of these diseases during the initial 2 years of follow-up. The extent to which this population comprises mild ARVC/D, CS, or other diseases is not clear.

Atrial tachycardias: Cause or effect with ablation of persistent atrial fibrillation?

INTRODUCTION: It is largely believed that atrial tachycardias (ATs) encountered during ablation of persistent atrial fibrillation (PsAF) are a byproduct of ablative lesions. We aimed to explore the alternative hypothesis that they may be a priori drivers of AF remaining masked until other AF sources are reduced or eliminated. METHODS AND RESULTS: Radiofrequency ablation of fibrillatory drivers mapped by electrocardiographic imaging (ECGI; ECVUE™, Cardioinsight Technologies, Cleveland, OH, USA) terminated PsAF in 198 (73%) out of 270 patients (61 ± 10 years, 9 ± 9 m). Two hundred and six ATs in 158 patients were subsequently mapped. Their anatomic relationship to the fibrillatory drivers prospectively identified by ECGI was then established. There were 26 (13%), 52 (25%), and 128 (62%) focal, localized, and macrore-entrant ATs, respectively. In focal/localized re-entrant ATs, 64 (82%) were terminated within an AF-driver region, in which 26 (81%) among 32 focal/localized ATs analyzed with 3-D-mapping system merged to driver map occurred from AF-driver regions in 1.0 ± 1.0 cm distance from the driver core. Importantly, there was no attempt at ablation of the associated AF-driver region in 25 of 64 (39%) of focal/localized re-entrant ATs. The sites of ATs origin generally had low-voltage, fractionated, and long-duration electrograms in AF. All but two focal/localized re-entrant ATs were successfully ablated. CONCLUSION: The majority of post-AF-ablation focal and localized re-entrant ATs originate from the region of prospectively established AF-driver regions. A third of these are localized to regions not subsequently submitted to ablation. These data suggest that many ATs exist, although not necessarily manifest independently, prior to ablation. They may have a role in the maintenance of PsAF in these individuals.

Distinctive Left Ventricular Activations Associated With ECG Pattern in Heart Failure Patients.

BACKGROUND: In contrast to patients with left bundle branch block (LBBB), heart failure patients with narrow QRS and nonspecific intraventricular conduction delay (NICD) display a relatively limited response to cardiac resynchronization therapy. We sought to compare left ventricular (LV) activation patterns in heart failure patients with narrow QRS and NICD to patients with LBBB using high-density electroanatomic activation maps. METHODS AND RESULTS: Fifty-two heart failure patients (narrow QRS [n=18], LBBB [n=11], NICD [n=23]) underwent 3-dimensional electroanatomic mapping with a high density of mapping points (387±349 LV). Adjunctive scar imaging was available in 37 (71%) patients and was analyzed in relation to activation maps. LBBB patients typically demonstrated (1) a single LV breakthrough at the septum (38±15 ms post-QRS onset); (2) prolonged right-to-left transseptal activation with absence of direct LV Purkinje activity; (3) homogeneous propagation within the LV cavity; and (4) latest activation at the basal lateral LV. In comparison, both NICD and narrow QRS patients demonstrated (1) multiple LV breakthroughs along the posterior or anterior fascicles: narrow QRS versus LBBB, 5±2 versus 1±1; P=0.0004; NICD versus LBBB, 4±2 versus 1±1; P=0.001); (2) evidence of early/pre-QRS LV electrograms with Purkinje potentials; (3) rapid propagation in narrow QRS patients and more heterogeneous propagation in NICD patients; and (4) presence of limited areas of late activation associated with LV scar with high interindividual heterogeneity. CONCLUSIONS: In contrast to LBBB patients, narrow QRS and NICD patients are characterized by distinct mechanisms of LV activation, which may predict poor response to cardiac resynchronization therapy.

Substrate-Based Ablation Versus Ablation Guided by Activation and Entrainment Mapping for Ventricular Tachycardia: A Systematic Review and Meta-Analysis.

INTRODUCTION: Substrate-based ablation for scar-related ventricular tachycardia (VT) has gained prominence: however, there is limited data comparing it to ablation guided predominantly by activation and entrainment mapping of inducible and hemodynamically tolerated VTs. We compared the acute procedural efficacy and outcomes of predominantly substrate-based ablation versus ablation guided predominantly by activation and entrainment mapping. METHODS AND RESULTS: Database searches through April 2016 identified 6 eligible studies (enrolling 403 patients, with 1 randomized study) comparing the 2 strategies. The relative risk of VT recurrence at follow-up was assessed as the primary outcome using a random-effects meta-analysis. Secondary endpoints of acute success (based on noninducibility of VT), procedural complications, and mortality were assessed using weighted mean difference with the random effects model. At a median follow-up of 18 months, the relative risk (RR) of VT recurrence was not significantly different with substrate-based versus activation/entrainment guided VT ablation (0.72, 95% confidence interval [CI] 0.44-1.18), P = 0.2). Acute success (RR 1.02, 95% CI 0.95-1.1, P = 0.6), procedural complications (RR 0.8, 95% CI 0.35-1.82, P = 0.5) cardiovascular mortality and total mortality did not differ significantly (RR 0.83, 95% CI 0.38-1.79, P = 0.6 and RR 0.76, 95% CI 0.36-1.59, P = 0.5, respectively). CONCLUSIONS: This meta-analysis demonstrates similar acute procedural efficacy, and complications, VT recurrence and mortality rates when comparing a predominantly substrate-based ablation strategy to a strategy guided predominantly by activation and entrainment mapping of inducible and hemodynamically tolerated VTs.

Image Integration to Guide Catheter Ablation in Scar-Related Ventricular Tachycardia.

BACKGROUND: Although multi-detector computed tomography (MDCT) and cardiac magnetic resonance (CMR) can assess the structural substrate of ventricular tachycardia (VT) in ischemic cardiomyopathy (ICM), non-ICM (NICM), and arrhythmogenic right ventricular cardiomyopathy (ARVC), the usefulness of systematic image integration during VT ablation remains undetermined. METHODS AND RESULTS: A total of 116 consecutive patients (67 ICM; 30 NICM; 19 ARVC) underwent VT ablation with image integration (MDCT 91%; CMR 30%; both 22%). Substrate was defined as wall thinning on MDCT and late gadolinium-enhancement on CMR in ICM/NICM, and as myocardial hypo-attenuation on MDCT in ARVC. This substrate was compared to mapping and ablation results with the endpoint of complete elimination of local abnormal ventricular activity (LAVA), and the impact of image integration on procedural management was analyzed. Imaging-derived substrate identified 89% of critical VT isthmuses and 85% of LAVA, and was more efficient in identifying LAVA in ICM and ARVC than in NICM (90% and 90% vs. 72%, P < 0.0001), and when defined from CMR than MDCT (ICM: 92% vs. 88%, P = 0.026, NICM: 88% vs. 72%, P < 0.001). Image integration motivated additional mapping and epicardial access in 57% and 33% of patients. Coronary and phrenic nerve integration modified epicardial ablation strategy in 43% of patients. The impact of image integration on procedural management was higher in ARVC/NICM than in ICM (P < 0.01), and higher in case of epicardial approach (P < 0.0001). CONCLUSIONS: Image integration is feasible in large series of patients, provides information on VT substrate, and impacts procedural management, particularly in ARVC/NICM, and in case of epicardial approach.

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.

Characterization of the Left-Sided Substrate in Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: The correlates of left ventricular (LV) substrate in arrhythmogenic right ventricular (RV) cardiomyopathy are largely unknown. METHODS AND RESULTS: Thirty-two patients with arrhythmogenic RV cardiomyopathy (47±14 years; 6 women) were included. RV and LV dysplasia were defined from multidetector computed tomography and cardiac magnetic resonance imaging. Arrhythmias were characterized as right-sided or left-sided on 12-lead ECG recordings at baseline and during isoproterenol testing. In 14 patients, the imaging substrate was compared with voltage mapping and local abnormal ventricular activity. Imaging abnormalities were found in 32 (100%) and 21 (66%) patients on the RV and LV, respectively, intramyocardial fat on multidetector computed tomography being the most sensitive feature. LV involvement related to none of the Task Force criteria. Right-sided arrhythmias were more frequent than left-sided arrhythmias (P=0.003) although the latter were more frequent in case of LV involvement (P=0.02). The agreement between low voltage and fat on multidetector computed tomography was high on the RV when using either endocardial unipolar or epicardial bipolar data (κ=0.82 and κ=0.78, respectively) but lower on the LV (κ=0.54 for epicardial bipolar). LV local abnormal ventricular activity was found in all patients with LV involvement, and none of the others. The density of local abnormal ventricular activity within fat areas was similar between the RV and LV (P=0.57). CONCLUSIONS: LV substrate is frequent in arrhythmogenic RV cardiomyopathy, but poorly identified by current diagnostic strategies. Left-sided arrhythmias are more frequent in case of LV involvement. LV fat hosts the same density of local abnormal ventricular activity as RV fat, but is less efficiently detected by voltage mapping. These results support the need for alternative diagnostic strategies to identify LV dysplasia.

nMARQ Ablation for Atrial Fibrillation: Results from a Multicenter Study.

BACKGROUND: nMARQ is a multipolar catheter designed to simultaneously ablate at multiple sites around the pulmonary vein (PV) circumference with a single radiofrequency application. We sought to define the safety and efficacy of atrial fibrillation (AF) ablation with the nMARQ catheter. METHODS: In a multicenter study, patients with drug-refractory AF were included. Procedural outcomes were documented at 1 year. RESULTS: 374 patients underwent PV isolation using nMARQ (age 60 ± 10 years, 264 male), of whom 263 patients had paroxysmal AF (PAF), while 111 patients had persistent AF. A total of 1,468 of 1,474 veins (99.6%) were isolated with the nMARQ catheter alone. Thirty-five (13%) PAF patients and 30 (27%) persistent AF patients underwent additional ablation at non-PV sites (2.4 ± 1.4 non-PV sites). Procedure time for PV isolation only was 1.9 ± 0.7 hours (fluoroscopy 24 ± 14 minutes). Procedure time for PV isolation and non-PV ablation was 2.4 ± 1.0 hours (fluoroscopy 30 ± 23 minutes). Major adverse events occurred in two patients (0.5%); one esophago-pericardial fistula and a second, mortality due to sepsis of unknown cause. One-year follow-up data were available in 65 (25%) PAF and 20 (18%) persistent AF patients. Forty-two (65%) PAF and 13 (65%) persistent AF patients were free of arrhythmia at 1 year. In patients undergoing repeat procedures (n = 17) the most frequent points of PV reconnection were: anterior RSPV, inferior RIPV, and superior LSPV. CONCLUSIONS: AF ablation with nMARQ is associated with short procedure times and high acute success rates. Further research is necessary to more clearly define long-term outcome.

Characteristics of ventricular tachycardia ablation in patients with continuous flow left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly used as a bridge to cardiac transplantation or as destination therapy. Patients with LVADs are at high risk for ventricular arrhythmias. This study describes ventricular arrhythmia characteristics and ablation in patients implanted with a Heart Mate II device. METHODS AND RESULTS: All patients with a Heart Mate II device who underwent ventricular arrhythmia catheter ablation at 9 tertiary centers were included. Thirty-four patients (30 male, age 58±10 years) underwent 39 ablation procedures. The underlying cardiomyopathy pathogenesis was ischemic in 21 and nonischemic in 13 patients with a mean left ventricular ejection fraction of 17%±5% before LVAD implantation. One hundred and ten ventricular tachycardias (VTs; cycle lengths, 230-740 ms, arrhythmic storm n=28) and 2 ventricular fibrillation triggers were targeted (25 transseptal, 14 retrograde aortic approaches). Nine patients required VT ablation <1 month after LVAD implantation because of intractable VT. Only 10/110 (9%) of the targeted VTs were related to the Heart Mate II cannula. During follow-up, 7 patients were transplanted and 10 died. Of the remaining 17 patients, 13 were arrhythmia-free at 25±15 months. In 1 patient with VT recurrence, change of turbine speed from 9400 to 9000 rpm extinguished VT. CONCLUSIONS: Catheter ablation of VT among LVAD recipients is feasible and reasonably safe even soon after LVAD implantation. Intrinsic myocardial scar, rather than the apical cannula, seems to be the dominant substrate.

Noninvasive mapping to guide atrial fibrillation ablation.

Atrial fibrillation (AF) is a dynamic rhythm. Noninvasive mapping overcomes many previous barriers to mapping such a dynamic rhythm, by providing a beat-to-beat, biatrial, panoramic view of the AF process. Catheter ablation of AF drivers guided by noninvasive mapping has yielded promising clinical results and has advanced understanding of the underlying pathophysiologic processes of this common heart rhythm disorder.

Noninvasive mapping of ventricular arrhythmias.

Several decades of research has led to the development of a 252-lead electrocardiogram-based three-dimensional imaging modality to refine noninvasive diagnosis and improve the management of heart rhythm disorders. This article reviews the clinical potential of this noninvasive mapping technique in identifying the sources of electrical disorders and guiding the catheter ablation of ventricular arrhythmias (premature ventricular beats and ventricular tachycardia). The article also briefly refers to the noninvasive electrical imaging of the arrhythmogenic ventricular substrate based on the electrophysiologic characteristics of postinfarction ventricular myocardium.

Postmyocarditis ventricular tachycardia in patients with epicardial-only scar: a specific entity requiring a specific approach.

BACKGROUND: Nonischemic cardiomyopathy is a heterogeneous condition providing a favorable substrate for ventricular tachycardia (VT). OBJECTIVE: The purpose of this study is to further characterize the substrate in a subset of postmyocarditis patients with epicardial-only scar. METHODS: Twelve postmyocarditis patients (11 male, 49 ± 14 years, left ventricular ejection fraction 49 ± 12%) with VT and epicardial-only scar were included for analysis comparing automatic high-amplitude normal activity (HANA) maps to manually adjusted maps of based on local abnormal ventricular activity (LAVA) electrograms when present. A combined endocardial (endo) and epicardial (epi) approach was used in 11/12 with usual bipolar/unipolar voltage thresholds and analyzed using image integration. RESULTS: A delayed enhancement MRI scar area of 52 cm(2) (38, 59) and multidetector CT wall thinning area of 18 cm(2) (14, 35) was found. Bipolar voltage substrate mapping (160 points [101, 239] endo, 553 points [232, 713] epi and LAVA were found only epicardially [443 LAVA points] in all) illustrated a low-voltage area of HANA: 1 cm(2) (0, 10) endo, 25 cm(2) (22, 39) epi and LAVA: 1 cm(2) (0, 10) endo, 39 cm(2) (28, 51) epi. Manual maps performed better than automatic maps for delineating low-voltage area with a higher overlap with scar area on delayed enhancement magnetic resonance imaging (DE-MRI; 76% [66, 94] vs. 45% [35, 62]; P = 0.04). In addition, manual voltage maps also showed a higher overlap with location of LAVA (LAVA in normal voltage area: 3% [0, 9] vs. 35% [32, 41]; P < 0.05). CONCLUSION: In postmyocarditis patients with epicardial-only scar, automatic voltage mapping may miss or minimize the electrical VT substrate. DE-MRI and manual LAVA-based voltage mapping are necessary to optimize scar delineation. Epicardial access is critical for mapping and ablation in this condition.

Expanding role of SK channels in cardiac electrophysiology.

The small conductance calcium-activated potassium (SK) channels are an important group of potassium-selective ion channels. SK channels display more pronounced expression in the atrium relative to the ventricle. Current evidence relating to the functional role of SK channels in the atria is conflicting and whether these channels contribute to atrial repolarization under physiological circumstances is a matter of debate. Multiple studies have, however, reported that SK channels are important mediators of proarrhythmogenic electrical remodeling in the atria. In keeping with their expression profile, SK channels do not appear to play a prominent role in ventricular repolarization. SK channels represent potentially attractive therapeutic targets for atrial fibrillation. A number of pharmacological modulators of SK channels have been tested in animal models of atrial fibrillation. However, these studies have also demonstrated inconsistent results and have raised important questions regarding the proarrhythmogenic potential of SK channel modulation. These findings have important implications for drug development. This review summarizes the role of SK channels in cardiac electrophysiology and discusses the potential role of these channels as therapeutic targets.

A novel trafficking-defective HCN4 mutation is associated with early-onset atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia, and a recent genome-wide association study identified the hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) as a novel AF susceptibility locus. HCN4 encodes for the cardiac pacemaker channel, and HCN4 mutations are associated with familial sinus bradycardia and AF. OBJECTIVE: The purpose of this study was to determine whether novel variants in the coding region of HCN4 contribute to the susceptibility for AF. METHODS: We sequenced the coding region of HCN4 for novel variants from 527 cases with early-onset AF from the Massachusetts General Hospital AF Study and 443 referents from the Framingham Heart Study. We used site-directed mutagenesis, cellular electrophysiology, immunocytochemistry, and confocal microscopy to functionally characterize novel variants. RESULTS: We found the frequency of novel coding HCN4 variants was 2-fold greater for individuals with AF (7 variants) compared to the referents (3 variants). We determined that of the 7 novel HCN4 variants in our AF cases, 1 (p.Pro257Ser, located in the amino-terminus adjacent to the first transmembrane spanning domain) did not traffic to cell membrane, whereas the remaining 6 were not functionally different from wild type. In addition, the 3 novel variants in our referents did not alter function compared to wild-type. Coexpression studies showed that the p.Pro257Ser mutant channel failed to colocalize with the wild-type HCN4 channel on the cell membrane. CONCLUSION: Our findings are consistent with HCN4 haploinsufficiency as the likely mechanism for early-onset AF in the p.Pro257Ser carrier.