Late life-threatening arrhythmia in patients with Brugada syndrome: Results from long-term follow-up in a large Japanese cohort.

INTRODUCTION: Most patients with Brugada syndrome (BrS) are first diagnosed in their 40s, with sudden cardiac death (SCD) often occurring in their 50s. Ventricular fibrillation (VF) may occur in some patients with BrS despite having been asymptomatic for a long period. This study aimed to assess the incidence and risk factors for late life-threatening arrhythmias in patients with BrS. METHODS: Patients with BrS (n = 523; mean age, 51 ± 13 years; male, n = 497) were enrolled. The risk of late life-threatening arrhythmia was investigated in 225 patients who had experienced no cardiac events (CEs: SCD or ventricular tachyarrhythmia) for at least 10 years after study enrollment. The incidence of CEs during the follow-up period was examined. RESULTS: During the follow-up of the 523 patients, 59 (11%) experienced CEs. The annual incidences of CEs were 2.87%, 0.77%, and 0.09% from study enrollment to 3, 3-10, and after 10 years, respectively. Among 225 patients who had experienced no CEs for at least 10 years after enrollment, four patients (1.8%) subsequently experienced CEs. Kaplan-Meier analysis revealed significant differences in the incidence of late CEs between patients with and without a history of symptoms (p = .032). The positive and negative predictive values of late CEs for the programmed electrical stimulation (PES) test were 2.9% and 100%, respectively. CONCLUSION: Our results suggest that patients with BrS who are asymptomatic and have no ventricular tachycardia/VF inducibility by PES are at extremely low risk of experiencing late life-threatening arrhythmias.

Advancements in Non-Dopaminergic Treatments for Schizophrenia: A Systematic Review of Pipeline Developments.

INTRODUCTION: Conventional antipsychotic drugs that attenuate dopaminergic neural transmission are ineffective in approximately one-third of patients with schizophrenia. This necessitates the development of non-dopaminergic agents. METHODS: A systematic search was conducted for completed phase II and III trials of compounds for schizophrenia treatment using the US Clinical Trials Registry and the EU Clinical Trials Register. Compounds demonstrating significant superiority over placebo in the primary outcome measure in the latest phase II and III trials were identified. Collateral information on the included compounds was gathered through manual searches in PubMed and press releases. RESULTS: Sixteen compounds were identified; four compounds (ulotaront, xanomeline/trospium chloride, vabicaserin, and roluperidone) were investigated as monotherapy and the remaining 12 (pimavanserin, bitopertin, BI 425809, encenicline, tropisetron, pregnenolone, D-serine, estradiol, tolcapone, valacyclovir, cannabidiol, and rimonabant) were examined as add-on therapy. Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin, bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for positive symptoms; roluperidone and pimavanserin were effective for negative symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and valacyclovir improved cognitive function. DISCUSSION: Compounds that function differently from existing antipsychotics may offer novel symptom-specific therapeutic strategies for patients with schizophrenia.

First-Line Catheter Ablation of Monomorphic Ventricular Tachycardia in Cardiomyopathy Concurrent With Defibrillator Implantation: The PAUSE-SCD Randomized Trial.

BACKGROUND: Catheter ablation as first-line therapy for ventricular tachycardia (VT) at the time of implantable cardioverter defibrillator (ICD) implantation has not been adopted into clinical guidelines. Also, there is an unmet clinical need to prospectively examine the role of VT ablation in patients with nonischemic cardiomyopathy, an increasingly prevalent population that is referred for advanced therapies globally. METHODS: We conducted an international, multicenter, randomized controlled trial enrolling 180 patients with cardiomyopathy and monomorphic VT with an indication for ICD implantation to assess the role of early, first-line ablation therapy. A total of 121 patients were randomly assigned (1:1) to ablation plus an ICD versus conventional medical therapy plus an ICD. Patients who refused ICD (n=47) were followed in a prospective registry after stand-alone ablation treatment. The primary outcome was a composite end point of VT recurrence, cardiovascular hospitalization, or death. RESULTS: Randomly assigned patients had a mean age of 55 years (interquartile range, 46-64) and left ventricular ejection fraction of 40% (interquartile range, 30%-49%); 81% were male. The underlying heart disease was ischemic cardiomyopathy in 35%, nonischemic cardiomyopathy in 30%, and arrhythmogenic cardiomyopathy in 35%. Ablation was performed a median of 2 days before ICD implantation (interquartile range, 5 days before to 14 days after). At 31 months, the primary outcome occurred in 49.3% of the ablation group and 65.5% in the control group (hazard ratio, 0.58 [95% CI, 0.35-0.96]; P=0.04). The observed difference was driven by a reduction in VT recurrence in the ablation arm (hazard ratio, 0.51 [95%CI, 0.29-0.90]; P=0.02). A statistically significant reduction in both ICD shocks (10.0% versus 24.6%; P=0.03) and antitachycardia pacing (16.2% versus 32.8%; P=0.04) was observed in patients who underwent ablation compared with control. No differences in cardiovascular hospitalization (32.0% versus. 33.7%; hazard ratio, 0.82 [95% CI, 0.43-1.56]; P=0.55) or mortality (8.9% versus 8.8%; hazard ratio, 1.40 [95% CI, 0.38-5.22]; P=0.62]) were observed. Ablation-related complications occurred in 8.3% of patients. CONCLUSIONS: Among patients with cardiomyopathy of varied causes, early catheter ablation performed at the time of ICD implantation significantly reduced the composite primary outcome of VT recurrence, cardiovascular hospitalization, or death. These findings were driven by a reduction in ICD therapies. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02848781.

Combined endo- and epicardial pace-mapping to localize ventricular tachycardia isthmus in ischaemic and non-ischaemic cardiomyopathy.

AIMS: A high-density pace-mapping can depict an abrupt transition in paced QRS morphology from a poor to excellent match, unmasking the critical component of ventricular tachycardia (VT) isthmus from the entrance to exit. We sought to assess pace-mapping at multiple sites within the endo- and epicardial scars to identify the VT isthmus in patients with ischaemic (ICM) and non-ischaemic cardiomyopathy (NICM). METHODS AND RESULTS: Colour-coded maps correlating to the percentage matches between 12-lead electrocardiograms during VT and pace-mapping [referred to as correlation score maps (CSMs)] were analysed. We studied 115 CSMs (80 endo- and 35 epicardial CSMs) in 37 patients (17 ICM, 20 NICM). The CSM with an abrupt change (AC) in pacemap score (AC-type) on the endocardium was more frequently observed in ICM than in NICM [11/39 (28%) vs. 1/41 (2%); P = 0.001]. Among 35 CSMs that were analysed by the combined endo- and epicardial mapping, 10 (29%) CSMs exhibited non-AC-type on the endocardium; however, AC-type was present on the opposite epicardium. Although 24 (69%) CSMs did not show AC-type on both the endocardium and epicardium, 16 of them had either an excellent (>90%) or poor (<0%) correlation score on either side, associated with isthmus exit or entrance, respectively. However, the remaining eight CSMs had neither excellent nor poor scores. CONCLUSION: The CSM may provide electrophysiological information to localize the endo- and epicardial VT isthmus. The absence of AC-type CSM on the endocardium, which is frequently observed in NICM, appears to indicate the sub-epicardial or intramural course of the critical isthmus.

Catheter ablation of ventricular tachycardia in dilated-phase hypertrophic cardiomyopathy: Substrate characterization and ablation outcome.

INTRODUCTION: Catheter ablation is a therapeutic option to suppress ventricular tachycardia (VT) in the setting of dilated-phase hypertrophic cardiomyopathy (DHCM). However, the characteristics of the arrhythmogenic substrate and the ablation outcome are not fully illustrated. METHOD: A total of 23 ablation procedures for drug-refractory sustained monomorphic VTs in 13 DHCM patients (60 ± 11 years, one female, the left ventricular [LV] ejection fraction 39% ± 9%, the LV mass index 156 ± 39 g/m2 ) were performed. The distribution of VT substrate as endocardial or epicardial/intramural was based on detailed mapping and ablation response during VT. RESULT: Two patients underwent ablation of sustained monomorphic VT that was not scar-mediated tachycardia. Of the remaining 11 patients, eight (73%) patients had VT substrate in the basal regions, most frequently at the epicardial and/or intramural basal antero-septum. None of the patients had VT substrate located at the LV inferolateral region. Ablation at the right ventricular septum and the aortic cusps was done in four and five patients, respectively. Other approaches including bipolar and chemical ablations, were done in three and two patients, respectively. Six (55%) out of 11 patients (two patients lost follow-up) had VT recurrence. All the six patients had basal substrate. However, anti-tachycardia pacing was sufficient for VT termination except in one patient. CONCLUSION: Catheter ablation of VT in patients with DHCM is challenging because of the predominant basal anteroseptal epicardial/intramural location of arrhythmogenic substrate. An ablation approach from multiple sites and/or adjunctive interventional techniques are often required.

The prebiotic fiber inulin ameliorates cardiac, adipose tissue, and hepatic pathology, but exacerbates hypertriglyceridemia in rats with metabolic syndrome.

Prebiotics ameliorate dysbiosis and influence metabolism and the immune system, but their effects on cardiovascular complications in metabolic disorders remain largely unknown. We here investigated the effects of the soluble fiber inulin on cardiac, adipose tissue, and hepatic pathology as well as on metabolic disorders in DahlS.Z-Leprfa/Leprfa (DS/obese) rats, an animal model of metabolic syndrome (MetS). DS/obese rats and their homozygous lean (DahlS.Z-Lepr+/Lepr+, or DS/lean) littermate controls were fed a purified diet containing 5% or 20% inulin from 9 to 13 wk of age. The high-fiber diet ameliorated hypertension, left ventricular inflammation, fibrosis and diastolic dysfunction; attenuated adipose tissue inflammation and fibrosis; and alleviated the elevation of interleukin-6 levels, without affecting insulin resistance, in DS/obese rats. In addition, high fiber intake ameliorated lipid accumulation, inflammation, and fibrosis; attenuated the reduction in AMPK activity; upregulated sterol regulatory element-binding protein-1c gene expression; and increased the expression of microsomal triglyceride transfer protein gene in the liver of DS/obese rats. It also mitigated increases in total and non-high-density lipoprotein cholesterol levels but increased the triglyceride concentration in serum in these rats. None of these parameters were affected by high dietary fiber in DS/lean rats. The proportion of regulatory T cells in adipose tissue was influenced by dietary fiber but not by genotype. Our results indicate that inulin exacerbates hypertriglyceridemia but alleviates hypertension and cardiac injury as well as adipose tissue and hepatic pathology in MetS rats.NEW & NOTEWORTHY Prebiotics ameliorate dysbiosis and influence metabolism and the immune system, but their effects on cardiovascular complications in metabolic disorders remain largely unknown. Inulin ameliorated hypertension, cardiac injury, and diastolic dysfunction without affecting obesity or insulin resistance in a rat model of metabolic syndrome. The favorable cardiac effects of inulin may be related to inhibition of systemic inflammation associated with a reduction in circulating interleukin-6 levels. Additionally, inulin exacerbated hypertriglyceridemia but alleviates adipose tissue and hepatic pathology in these animals, as well as increased the number of regulatory T cells in adipose tissue.

Catheter Ablation of Refractory Ventricular Fibrillation Storm After Myocardial Infarction.

BACKGROUND: Ventricular fibrillation (VF) storm after myocardial infarction (MI) is a life-threatening condition that necessitates multiple defibrillations. Catheter ablation is a potentially effective treatment strategy for VF storm refractory to optimal medical treatment. However, its impact on patient survival has not been verified in a large population. METHODS: We conducted a multicenter, retrospective observational study involving consecutive patients who underwent catheter ablation of post-MI refractory VF storm without preceding monomorphic ventricular tachycardia. The target of ablation was the Purkinje-related ventricular extrasystoles triggering VF. The primary outcome was in-hospital and long-term mortalities. Univariate logistic regression and Cox proportional-hazards analysis were used to evaluate clinical characteristics associated with in-hospital and long-term mortalities, respectively. RESULTS: One hundred ten patients were enrolled (age, 65±11years; 92 men; left ventricular ejection fraction, 31±10%). VF storm occurred at the acute phase of MI (4.5±2.5 days after the onset of MI during the index hospitalization for MI) in 43 patients (39%), the subacute phase (>1 week) in 48 (44%), and the remote phase (>6 months) in 19 (17%). The focal triggers were found to originate from the scar border zone in 88 patients (80%). During in-hospital stay after ablation, VF storm subsided in 92 patients (84%). Overall, 30 (27%) in-hospital deaths occurred. The duration from the VF occurrence to the ablation procedure was associated with in-hospital mortality (odds ratio for each 1-day increase, 1.11 [95% CI, 1.03-1.20]; P=0.008). During follow-up after discharge from hospital, only 1 patient developed recurrent VF storm. However, 29 patients (36%) died, with a median survival time of 2.2 years (interquartile range, 1.2-5.5 years). Long-term mortality was associated with left ventricular ejection fraction <30% (hazard ratio, 2.54 [95% CI, 1.21-5.32]; P=0.014), New York Heart Association class ≥III (hazard ratio, 2.68 [95% CI, 1.16-6.19]; P=0.021), a history of atrial fibrillation (hazard ratio, 3.89 [95% CI, 1.42-10.67]; P=0.008), and chronic kidney disease (hazard ratio, 2.74 [95% CI, 1.15-6.49]; P=0.023). CONCLUSIONS: In patients with MI presenting with focally triggered VF storm, catheter ablation of culprit triggers is lifesaving and appears to be associated with short- and long-term freedom from recurrent VF storm. Mortality over the long-term follow-up is associated with the severity of underlying cardiovascular disease and comorbidities in this specific patient population.

Preprocedural restoration of sinus rhythm and left atrial strain predict outcomes of catheter ablation for long-standing persistent atrial fibrillation.

INTRODUCTION: Catheter ablation (CA) for long-standing persistent atrial fibrillation (LS-AF) remains challenging. We aimed to explore whether sinus rhythm (SR) restoration and left atrium (LA) function after pretreatment with antiarrhythmic drugs (AAD's) and electrical cardioversion (ECV) predict procedural outcomes. METHODS AND RESULTS: We included 100 consecutive patients with LS-AF who were treated with AAD/ECV for at least 3 months before CA. The echocardiographic LA strain during reservoir phase (LASr) was assessed after pretreatment as a marker of LA fibrosis. The recurrence was recorded for ≥1 year after the last procedure. During a 34 ± 16-month follow-up period, the single and multiple procedures and pharmaceutically assisted success rates were 40% and 71%, respectively. Patients with preprocedural SR restoration and higher LASr showed a significantly higher recurrence-free probability after the last CA (logrank P = .001 and P < .001, respectively). Failure of preprocedural SR restoration and LASr ≤8.6% were independently associated with recurrence after the last CA (hazard ratio [HR]: 3.13, 95% confidence interval [CI]: 1.42-6.91, P = .005; HR: 3.89, 95% CI: 1.65-9.17, P = .002, respectively). These parameters added incrementally to the predictive value of AF duration and LA dilatation (P = .03 and P = .002, respectively) and improved the recurrence-risk stratification (net reclassification improvement = 0.39; 95% CI = 0.13-0.65; P = .003). CONCLUSION: In patients with LS-AF, the inability to restore SR and lower LASr after AAD/ECV treatment independently and incrementally predicts the recurrence after CA. These findings might be useful for determining LS-AF ablation candidates.

The 'double transition': a novel electrocardiogram sign to discriminate posteroseptal accessory pathways ablated from the right endocardium from those requiring a left-sided or epicardial coronary venous approach.

AIMS: The precise localization of manifest posteroseptal accessory pathways (APs) often poses diagnostic challenges considering that a small area may encompass AP that may be ablated from the right or left endocardium, or epicardially within the coronary sinus (CS). We sought to explore whether the QRS transition pattern in the precordial lead may help to discriminate the necessary ablation approach. METHODS AND RESULTS: Consecutive patients who underwent a successful ablation of a single manifest AP over a 5-year period were included. Standard 12-lead electrocardiograms were reviewed. A total of 273 patients were identified. Mean age was 31 ± 15 years and 62% were male. Of the 110 identified posteroseptal AP, 64 were ablated from the right endocardium, 33 from the left endocardium, and 13 inside the CS. While a normal precordial QRS transition was most often observed, a subset of 33 patients presented an atypical 'double transition' pattern which specifically identified right endocardial AP. The combination of a q wave in V1 with a proportion of the positive QRS component in V1 < V2 > V3, predicted a right endocardial AP with a 100% specificity. In case of a positive QRS sum in V2, this 'double transition' pattern predicted a posteroseptal right endocardial AP with 99.5% specificity and 44% sensitivity. The positive predictive value was 97%. The only false positive was a midseptal AP. In the case of a negative or isoelectric QRS sum in V2, APs were located more laterally on the tricuspid annulus. CONCLUSION: The combination of a q wave in V1 with a double QRS transition pattern in the precordial leads is highly specific of a right endocardial AP and rules out the need for CS or left-sided mapping.

Stepwise approach to induce infrequent premature ventricular complex using bolus isoproterenol and epinephrine infusion.

BACKGROUND: Paucity of a premature ventricular complex (PVC) during ablation procedures may occur and be associated with a lower success rate. Isoproterenol (ISP) injections are commonly used to induce PVC; however, the induced tachycardia sometimes prevents the appearance of PVC. Epinephrine (EPI) administration may be an alternative strategy to induce PVC due to its smaller effect on heart rate (HR). This study sought to examine the electrophysiological impact of EPI injection, with a stepwise induction protocol, for infrequent intraprocedural PVC. METHODS: We studied 78 consecutive patients who underwent catheter ablation of idiopathic frequent PVC. If no PVC was observed at the beginning of the procedure, ISP (10 µg) was injected. If clinical PVC was not induced by ISP administration, EPI (10 µg) was injected. RESULTS: Of 18 patients without PVC at baseline, ISP injection induced PVC in five patients. Of the remaining 13 patients, EPI injection successfully induced PVC in seven patients (53%). The maximum HR and increments of HR after EPI injection were significantly lower than those after ISP injection (99 ± 15 vs 137 ± 15 bpm, P = .001; 22 ± 10 vs 53 ± 12 bpm, P < .001, respectively). There were no complications related to the induction protocol. CONCLUSION: EPI injection following ISP injection is an effective and safe stepwise approach for the induction of infrequent PVC in the electrophysiology laboratory. It is hypothesized that α- and ß-adrenergic receptor stimulation by EPI injections, with reduced HR acceleration compared to that with ISP injections, may result in the successful induction of PVC.

Impact of coronary artery disease and revascularization on recurrence of atrial fibrillation after catheter ablation: Importance of ischemia in managing atrial fibrillation.

INTRODUCTION: There are few studies analyzing the association between the presence of coronary artery disease (CAD) and recurrence of atrial fibrillation (AF). This study evaluated the clinical impact of concomitant CAD and coronary revascularization on the recurrence of AF after catheter ablation. METHODS AND RESULTS: From April 2008 to December 2015, 700 consecutive patients were treated with pulmonary vein isolation for AF as the initial procedure. Of those, 681 patients who simultaneously underwent coronary angiography were investigated. Patients with at least one coronary stenosis (≥70%) were classified as having obstructive CAD. Of 681 patients, 90 patients had CAD and 42 patients underwent percutaneous coronary intervention (PCI) for lesions with perfusion abnormalities on single-photon emission tomography. The recurrence of AF was significantly more frequent in patients with CAD (56%) than in those without CAD (39%) (P = .0011). On multivariable analysis, the predictors of AF recurrence were persistent or long-standing persistent AF [hazard ratio (HR): 1.36; 95% confidence interval (CI): 1.04-1.77; P = .023], left atrial diameter (HR: 1.04; 95% CI: 1.02-1.06; P < .0001), and concomitant CAD (HR: 1.45; 95% CI: 1.05-1.97; P = .024). The recurrence of AF in patients with PCI (38%) was significantly lower than in those without PCI (72%) (P = .0006), and E/E' significantly improved in patients with PCI (71%) than in those without PCI (42%; P = .001). Performing PCI for concomitant CAD significantly reduced AF recurrence (HR: 0.39; 95% CI: 0.20-0.72; P = .002). CONCLUSION: Patients with CAD had a significantly higher rate of AF recurrence than those without CAD. Coronary revascularization may reduce the recurrence of AF with improvement of left ventricular diastolic function.

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.

Driver domains in persistent atrial fibrillation.

BACKGROUND: Specific noninvasive signal processing was applied to identify drivers in distinct categories of persistent atrial fibrillation (AF). METHODS AND RESULTS: In 103 consecutive patients with persistent AF, accurate biatrial geometry relative to an array of 252 body surface electrodes was obtained from a noncontrast computed tomography scan. The reconstructed unipolar AF electrograms acquired at bedside from multiple windows (duration, 9±1 s) were signal processed to identify the drivers (focal or reentrant activity) and their cumulative density map. The driver domains were catheter ablated by using AF termination as the procedural end point in comparison with the stepwise-ablation control group. The maps showed incessantly changing beat-to-beat wave fronts and varying spatiotemporal behavior of driver activities. Reentries were not sustained (median, 2.6 rotations lasting 449±89 ms), meandered substantially but recurred repetitively in the same region. In total, 4720 drivers were identified in 103 patients: 3802 (80.5%) reentries and 918 (19.5%) focal breakthroughs; most of them colocalized. Of these, 69% reentries and 71% foci were in the left atrium. Driver ablation alone terminated 75% and 15% of persistent and long-lasting AF, respectively. The number of targeted driver regions increased with the duration of continuous AF: 2 in patients presenting in sinus rhythm, 3 in AF lasting 1 to 3 months, 4 in AF lasting 4 to 6 months, and 6 in AF lasting longer. The termination rate sharply declined after 6 months. The mean radiofrequency delivery to AF termination was 28±17 minutes versus 65±33 minutes in the control group (P<0.0001). At 12 months, 85% patients with AF termination were free from AF, similar to the control population (87%,); P=not significant. CONCLUSIONS: Persistent AF in early months is maintained predominantly by drivers clustered in a few regions, most of them being unstable reentries.

Automated Quantification of Right Ventricular Fat at Contrast-enhanced Cardiac Multidetector CT in Arrhythmogenic Right Ventricular Cardiomyopathy.

PURPOSE: To evaluate an automated method for the quantification of fat in the right ventricular (RV) free wall on multidetector computed tomography (CT) images and assess its diagnostic value in arrhythmogenic RV cardiomyopathy (ARVC). MATERIALS AND METHODS: This study was approved by the institutional review board, and all patients gave informed consent. Thirty-six patients with ARVC (mean age ± standard deviation, 46 years ± 15; seven women) were compared with 36 age- and sex-matched subjects with no structural heart disease (control group), as well as 36 patients with ischemic cardiomyopathy (ischemic group). Patients underwent contrast material-enhanced electrocardiography-gated cardiac multidetector CT. A 2-mm-thick RV free wall layer was automatically segmented and myocardial fat, expressed as percentage of RV free wall, was quantified as pixels with attenuation less than -10 HU. Patient-specific segmentations were registered to a template to study fat distribution. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic value of fat quantification by using task force criteria as a reference. RESULTS: Fat extent was 16.5% ± 6.1 in ARVC and 4.6% ± 2.7 in non-ARVC (P < .0001). No significant difference was observed between control and ischemic groups (P = .23). A fat extent threshold of 8.5% of RV free wall was used to diagnose ARVC with 94% sensitivity (95% confidence interval [CI]: 82%, 98%) and 92% specificity (95% CI: 83%, 96%). This diagnostic performance was higher than the one for RV volume (mean area under the ROC curve, 0.96 ± 0.02 vs 0.88 ± 0.04; P = .009). In patients with ARVC, fat correlated to RV volume (R = 0.63, P < .0001), RV function (R = -0.67, P = .001), epsilon waves (R = 0.39, P = .02), inverted T waves in V1-V3 (R = 0.38, P = .02), and presence of PKP2 mutations (R = 0.59, P = .02). Fat distribution differed between patients with ARVC and those without, with posterolateral RV wall being the most ARVC-specific area. CONCLUSION: Automated quantification of RV myocardial fat on multidetector CT images is feasible and performs better than RV volume in the diagnosis of ARVC. Online supplemental material is available for this article.

Left atrial appendage flow velocity after successful ablation of persistent atrial fibrillation: clinical perspective from transesophageal echocardiographic assessment during sinus rhythm.

BACKGROUND: Left atrial appendage flow velocity (LAAFV) is a predictor of thromboembolism in atrial fibrillation (AF) patients, as well as CHA2DS2-VASc score. However, little is known about LAAFV in sinus rhythm (SR) after catheter ablation. The aim of this study was to determine clinical predictors of low LAAFV in patients in whom stable SR had been maintained after catheter ablation for persistent AF. METHODS: The study comprised 104 patients with persistent AF (median AF duration 24 months) in whom SR had been achieved and maintained for at least 6 months after the final ablation procedure. Transesophageal echocardiography was performed to assess LAAFV during SR after ablation. Lower LAAFV was defined as ≤40 cm/s. RESULTS: Mean LAAFV before ablation was 29 ± 11 cm/s (range 10-67 cm/s). In 23 (22%) patients, LAAFV remained low even after being in SR for at least 6 months. Multiple logistic regression analysis showed that CHA2DS2-VASc scores of ≥2 (odds ratio 2.18, 95% CI 1.19-3.99, P = .012) was an independent predictor of lower LAAFV after successful ablation. Seventeen (74%) of the 23 patients with low LAAFV during SR presented CHA2DS2-VASc scores of ≥2 complicated by spontaneous echo contrast during AF. CONCLUSIONS: Long-term maintenance of SR after catheter ablation for persistent AF does not guarantee LAAFV recovery. The CHA2DS2-VASc score appears to predict poor recovery of LAAFV. Further studies are necessary to confirm the usefulness of LAAFV during SR as a surrogate marker predicting thromboembolism in patients after AF ablation.

Impact of Substrate-Based Ablation of Ventricular Tachycardia on Cardiac Mortality in Patients With Implantable Cardioverter-Defibrillators.

INTRODUCTION: This study sought to determine if the acute procedural outcome of ventricular tachycardia (VT) substrate ablation is associated with a mortality benefit in patients with implantable cardioverter-defibrillators (ICD). METHODS AND RESULTS: A total of 195 ICD recipients (65 ± 11years) with ischemic or nonischemic dilated cardiomyopathy underwent substrate-based ablation targeting elimination of local abnormal ventricular activities (LAVA). Acute procedural success, which was defined as elimination of all identified LAVA in addition to the lack of VT inducibility, was achieved in 95 (49%) patients. During a median follow-up of 23 months, patients with acute procedure success had a significantly lower incidence of ICD shocks compared to those with ablation failure (8% vs. 30%, P < 0.001). In multivariate analysis, acute procedural success was associated with a lower risk of VT recurrence (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.18-0.49, P < 0.001) and all-cause mortality (HR 0.32, 95% CI 0.17-0.60, P < 0.001). While the impact of ablation success on mortality was not statistically significant in patients with LVEF > 35% (HR 0.45, 95% CI 0.15-1.34, P = 0.15) and those with NYHA class I/II (HR 0.63, 95% CI 0.29-1.40, P = 0.26), it was marked in patients with LVEF ≤ 35% (HR 0.30, 95% CI 0.14-0.62, P = 0.001) and NYHA class III/IV (HR 0.17, 95% CI 0.05-0.57, P = 0.004). CONCLUSIONS: LAVA elimination in addition to VT noninducibility as a procedural outcome for substrate-based ablation is associated with reduced mortality and better VT-free survival during follow-up. This prognostic benefit may be most pronounced in patients with severe heart failure as indicated by severely depressed LV function and NYHA class III/IV symptoms.

Length of the Mitral Isthmus But Not Anatomical Location of Ablation Line Predicts Bidirectional Mitral Isthmus Block in Patients Undergoing Catheter Ablation of Persistent Atrial Fibrillation: A Randomized Controlled Trial.

INTRODUCTION: Mitral isthmus (MI) ablation is an effective option in patients undergoing ablation for persistent atrial fibrillation (AF). Achieving bidirectional conduction block across the MI is challenging, and predictors of MI ablation success remain incompletely understood. We sought to determine the impact of anatomical location of the ablation line on the efficacy of MI ablation. METHODS AND RESULTS: A total of 40 consecutive patients (87% male; 54 ± 10 years) undergoing stepwise AF ablation were included. MI ablation was performed in sinus rhythm. MI ablation was performed from the left inferior PV to either the posterior (group 1) or the anterolateral (group 2) mitral annulus depending on randomization. The length of the MI line (measured with the 3D mapping system) and the amplitude of the EGMs at 3 positions on the MI were measured in each patient. MI block was achieved in 14/19 (74%) patients in group 1 and 15/21 (71%) patients in group 2 (P = NS). Total MI radiofrequency time (18 ± 7 min vs. 17 ± 8 min; P = NS) was similar between groups. Patients with incomplete MI block had a longer MI length (34 ± 6 mm vs. 24 ± 5 mm; P < 0.001), a higher bipolar voltage along the MI (1.75 ± 0.74 mV vs. 1.05 ± 0.69 mV; P < 0.01), and a longer history of continuous AF (19 ± 17 months vs. 10 ± 10 months; P < 0.05). In multivariate analysis, decreased length of the MI was an independent predictor of successful MI block (OR 1.5; 95% CI 1.1-2.1; P < 0.05). CONCLUSIONS: Increased length but not anatomical location of the MI predicts failure to achieve bidirectional MI block during ablation of persistent AF.

Ventricular arrhythmias with superior axis originating from the left ventricular septum: electrocardiographic characteristics predicting successful ablation and insights into their mechanism-observations from a small series of patients.

AIMS: This study aimed to evaluate the electrocardiographic characteristics and predictors of successful ablation for ventricular arrhythmias (VAs) with superior axis originating in the ventricular septum. METHODS AND RESULTS: This study included 385 consecutive patients with VAs undergoing radiofrequency ablation (RFA). Of these, 14 patients (3.7%) were identified who had VAs with superior axis that were mapped to and ablated at the left ventricular (LV) septum. These patients were classified into two groups, successful (n = 9, Success-RFA) and failed (n = 5, Fail-RFA) ablation. The QRS duration of the VAs was longer in the Success-RFA than the Fail-RFA [median (25%, 75% quartile), 140 (134, 149) vs. 128 (116, 132) ms; P = 0.007]. In the Success-RFA, the QRS morphology in lead V1 exhibited qR or rSR (r < 0.2 mV) pattern. In the Fail-RFA, QRS in lead V1 demonstrated an initial R-wave of ≥0.2 mV except for one patient who demonstrated a qR pattern. The initial R-wave amplitude of <0.2 mV in lead V1 identified successful ablation cases with 100% sensitivity and 80% specificity. The magnitude of the initial R-wave amplitude in lead V1 could be related to the originating site's depth within the septal tissue, which could also explain the RFA results. CONCLUSION: Four percent of VA patients had superior axis on electrocardiogram and foci that mapped to the LV septum, two-thirds of which were successfully ablated. The initial R-wave amplitude of <0.2 mV in lead V1 identified RFA success with high sensitivity and specificity.

Catheter ablation of atrial tachyarrhythmias causing inappropriate implantable cardioverter-defibrillator shocks.

AIMS: Inappropriate shocks have been an important issue post-implantable cardioverter-defibrillator (ICD) implantation. Moreover, inappropriate ICD shocks are associated with increased mortality. The objective of this study was to evaluate the feasibility of catheter ablation therapy for atrial tachyarrhythmias (ATa) responsible for inappropriate ICD shocks. METHODS AND RESULTS: Among 108 consecutive patients who underwent ICD implantations, 22, 5, and 3 experienced inappropriate ICD shocks due to ATa, sinus tachycardia, and T-wave oversensing, respectively. Among the 22 patients with ATa, 18 patients (55 ± 10 years, 15 men, structural heart disease in 9) underwent catheter ablation of ATa causing inappropriate shocks. The median duration between the ICD implantation and first inappropriate shock was 10.0 (3.0-24.5) months. The ATa were atrial fibrillation (AF), atrial flutter (AFL), and atrioventricular nodal reentrant tachycardia in 14, 2, and 2 patients, respectively. One patient underwent an atrioventricular nodal ablation for persistent AF associated with a venous anomaly. Among 13 patients who underwent pulmonary vein antrum isolation, 10 (76.9%) were free from AF for a median of 21.0 (13-37.3) months after an average of 1.3 ± 0.5 procedures. In four patients with AFL or a supraventricular tachycardia, none had any arrhythmia recurrence for a median of 6.0 (3.3-93.5) months after a cavotricuspid isthmus or slow pathway ablation, respectively. There were no procedural complications. During the median follow-up of 19.0 (9.5-37.3) months after the last procedure, no patients experienced any inappropriate shocks. CONCLUSION: Catheter ablation is a feasible therapeutic option for treating ATa responsible for inappropriate shock(s) in patients with ICD.