Project description:Previous studies suggest that magnetic resonance imaging with late gadolinium enhancement (LGE) may identify slowly conducting tissues in scar-related ventricular tachycardia (VT).To test the feasibility of image-based simulation based on LGE to estimate ablation targets in VT.We conducted a retrospective study in 13 patients who had preablation magnetic resonance imaging for scar-related VT ablation. We used image-based simulation to induce VT and estimate target regions according to the simulated VT circuit. The estimated target regions were coregistered with the LGE scar map and the ablation sites from the electroanatomical map in the standard ablation approach.In image-based simulation, VT was inducible in 12 (92.3%) patients. All VTs showed macroreentrant propagation patterns, and the narrowest width of estimated target region that an ablation line should span to prevent VT recurrence was 5.0 ± 3.4 mm. Of 11 patients who underwent ablation, the results of image-based simulation and the standard approach were consistent in 9 (82%) patients, where ablation within the estimated target region was associated with acute success (n = 8) and ablation outside the estimated target region was associated with failure (n = 1). In 1 (9%) case, the results of image-based simulation and the standard approach were inconsistent, where ablation outside the estimated target region was associated with acute success.The image-based simulation can be used to estimate potential ablation targets of scar-related VT. The image-based simulation may be a powerful noninvasive tool for preprocedural planning of ablation procedures to potentially reduce the procedure time and complication rates.
Project description:KCNE5 is an X-linked gene encoding KCNE5, an ancillary subunit to voltage-gated potassium (KV) channels. Human KCNE5 mutations are associated with atrial fibrillation (AF)- and Brugada syndrome (BrS)-induced cardiac arrhythmias that can arise from increased potassium current in cardiomyocytes. Seeking to establish underlying molecular mechanisms, we created and studied Kcne5 knockout ( Kcne5-/0) mice. Intracardiac ECG revealed that Kcne5 deletion caused ventricular premature beats, increased susceptibility to induction of polymorphic ventricular tachycardia (60 vs. 24% in Kcne5+/0 mice), and 10% shorter ventricular refractory period. Kcne5 deletion increased mean ventricular myocyte KV current density in the apex and also in the subpopulation of septal myocytes that lack fast transient outward current ( Ito,f). The current increases arose from an apex-specific increase in slow transient outward current-1 ( IKslow,1) (conducted by KV1.5) and Ito,f (conducted by KV4) and an increase in IKslow,2 (conducted by KV2.1) in both apex and septum. Kcne5 protein localized to the intercalated discs in ventricular myocytes, where KV2.1 was also detected in both Kcne5-/0 and Kcne5+/0 mice. In HL-1 cardiac cells and human embryonic kidney cells, KCNE5 and KV2.1 colocalized at the cell surface, but predominantly in intracellular vesicles, suggesting that Kcne5 deletion increases IK,slow2 by reducing KV2.1 intracellular sequestration. The human AF-associated mutation KCNE5-L65F negative shifted the voltage dependence of KV2.1-KCNE5 channels, increasing their maximum current density >2-fold, whereas BrS-associated KCNE5 mutations produced more subtle negative shifts in KV2.1 voltage dependence. The findings represent the first reported native role for Kcne5 and the first demonstrated Kcne regulation of KV2.1 in mouse heart. Increased KV current is a manifestation of KCNE5 disruption that is most likely common to both mouse and human hearts, providing a plausible mechanistic basis for human KCNE5-linked AF and BrS.-David, J.-P., Lisewski, U., Crump, S. M., Jepps, T. A., Bocksteins, E., Wilck, N., Lossie, J., Roepke, T. K., Schmitt, N., Abbott, G. W. Deletion in mice of X-linked, Brugada syndrome- and atrial fibrillation-associated Kcne5 augments ventricular KV currents and predisposes to ventricular arrhythmia.
Project description:BackgroundAortic root dilatation and-dissection and mitral valve prolapse are established cardiovascular manifestations in Marfan syndrome (MFS). Heart failure and arrhythmic sudden cardiac death have emerged as additional causes of morbidity and mortality.MethodsTo characterize myocardial dysfunction and arrhythmia in MFS we conducted a prospective longitudinal case-control study including 86 patients with MFS (55.8% women, mean age 36.3 yr-range 13-70 yr-) and 40 age-and sex-matched healthy controls. Cardiac ultrasound, resting and ambulatory ECG (AECG) and NT-proBNP measurements were performed in all subjects at baseline. Additionally, patients with MFS underwent 2 extra evaluations during 30 ± 7 months follow-up. To study primary versus secondary myocardial involvement, patients with MFS were divided in 2 groups: without previous surgery and normal/mild valvular function (MFS-1; N = 55) and with previous surgery or valvular dysfunction (MFS-2; N = 31).ResultsCompared to controls, patients in MFS-1 showed mild myocardial disease reflected in a larger left ventricular end-diastolic diameter (LVEDD), lower TAPSE and higher amount of (supra) ventricular extrasystoles [(S)VES]. Patients in MFS-2 were more severely affected. Seven patients (five in MFS-2) presented decreased LV ejection fraction. Twenty patients (twelve in MFS-2) had non-sustained ventricular tachycardia (NSVT) in at least one AECG. Larger LVEDD and higher amount of VES were independently associated with NSVT.ConclusionOur study shows mild but significant myocardial involvement in patients with MFS. Patients with previous surgery or valvular dysfunction are more severely affected. Evaluation of myocardial function with echocardiography and AECG should be considered in all patients with MFS, especially in those with valvular disease and a history of cardiac surgery.
Project description:Background and objectivesThere is little emphasis on the efficacy of catheter ablation for ventricular arrhythmia (VA) when using VA burden reduction as a marker for success. We examined the efficacy of catheter ablation using VA burden, rather than VA recurrence as a marker of success, following catheter ablation of structural heart disease (SHD) related VA.MethodsCatheter ablation of SHD related VA was performed at a single centre over 4-years. VA episodes and implantable cardioverter defibrillator (ICD) therapies were recorded over the 6-months before and after final ablation. Outcomes were reported in terms of burden reduction and compared to singular VA recurrence.ResultsOverall, 108 patients were included in the study. Mean age 64.2±13.9 years, 86% male, mean left ventricular ejection fraction (LVEF) 42±16%. Median VA episodes and ICD therapy were significantly reduced after ablation (VA before: 10 [interquartile range, IQR: 2-38] vs. VA after: 0 [IQR: 0-2], p<0.001; anti-tachycardia pacing [ATP] before: 16 (IQR: 1.5-57) vs. ATP after: 0 [IQR: 0-2], p<0.001; shocks before: 1 [IQR: 0-5] vs. shocks after: 0 [IQR: 0-0], p<0.001). Procedural success at 6-months was significantly higher when considering ≥75% reduction in VA burden, rather than a singular VA-free survival (83% vs. 67%, p=0.001).ConclusionsThe vast majority (>80%) of patients achieve reduction in VA burden (≥75% reduction) after catheter ablation for VA. This data suggests that catheter ablation is highly therapeutic when procedure success is defined as reduction in VA, rather than using a single VA recurrence as a metric for failure.
Project description:Background: RFA is a well-established treatment for symptomatic patients with AF. However, the success rate of a single procedure is low. We aimed to investigate the association between the risk of recurrence of atrial fibrillation (AF) after a single radiofrequency ablation (RFA) procedure and cardiac neurohormonal function, left atrial (LA) mechanical function as well as proteins related to inflammation, fibrosis, and apoptosis. Methods and Results: We studied 189 patients undergoing RFA between January 2012 and April 2014, with a follow-up period of 12 months. A logistic regression analysis was performed to investigate the association between pre-ablation LA emptying fraction (LAEF), MR-proANP, Caspase-8 (CASP8), Neurotrophin-3 (NT3), and the risk for recurrence of AF after a single RFA procedure. 119 (63.0%) patients had a recurrence during a mean follow-up of 402 ± 73 days. An increased risk of recurrence was associated with: Elevated MR-proANP (fourth quartile vs. first quartile: HR, 2.80 (95% CI, 1.14-6.90]; P = 0.025); Low LAEF (fourth quartile vs. first quartile: hazard ratio [HR], 2.41 [95% CI, 1.01-5.79]; P = 0.045); Elevated CASP8 (fourth quartile vs. first quartile: HR 12.198 95% CI 2.216-67.129; P = 0.004); Elevated NT-3 (fourth quartile vs. first quartile: HR 7.485 95% CI 1.353-41.402; P = 0.021). In a receiver operating characteristic curve analysis, the combination of MR-proANP, CASP8, and NT3 produced an area under the curve of 0.819; CI 95% (0.710-0.928). Conclusions: Patients with better LA mechanical function and lower levels of atrial neurohormones as well as of proteins related to fibrosis and apoptosis, have a better outcome after an RFA procedure. Unique identifier: No. NCT01553045 (https://clinicaltrials.gov/ct2/show/NCT01553045?term=NCT01553045&rank=1).
Project description:BACKGROUND:Arrhythmia ablation with current techniques is not universally successful. Inadequate ablation lesion formation may be responsible for some arrhythmia recurrences. Periprocedural visualization of ablation lesions may identify inadequate lesions and gaps to guide further ablation and reduce risk of arrhythmia recurrence. METHODS:This feasibility study assessed acute postprocedure ablation lesions by MRI, and correlated these findings with clinical outcomes. Ten pediatric patients who underwent ventricular tachycardia ablation were transferred immediately postablation to a 1.5T MRI scanner and late gadolinium enhancement (LGE) imaging was performed to characterize ablation lesions. Immediate and mid-term arrhythmia recurrences were assessed. RESULTS:Patient characteristics include median age 14 years (1-18 years), median weight 52 kg (11-81 kg), normal cardiac anatomy (n = 6), d-transposition of great arteries post arterial switch repair (n = 2), anomalous coronary artery origin post repair (n = 1), and cardiac rhabdomyoma (n = 1). All patients underwent radiofrequency catheter ablation of ventricular arrhythmia with acute procedural success. LGE was identified at the reported ablation site in 9/10 patients, all arrhythmia-free at median 7 months follow-up. LGE was not visible in 1 patient who had recurrence of frequent premature ventricular contractions within 2 hours, confirmed on Holter at 1 and 21 months post procedure. CONCLUSIONS:Ventricular ablation lesion visibility by MRI in the acute post procedure setting is feasible. Lesions identifiable with MRI may correlate with clinical outcomes. Acute MRI identification of gaps or inadequate lesions may provide the unique temporal opportunity for additional ablation therapy to decrease arrhythmia recurrence.
Project description:ObjectiveTo evaluate the effectiveness and safety of totally thoracoscopic ablation (TTA) in patients with left ventricular (LV) dysfunction for treatment of atrial fibrillation (AF) refractory to antiarrhythmic drug (AAD) therapy.MethodsBetween January 2012 and December 2018, 31 patients underwent TTA with drug-refractory AF and preoperative left ventricular ejection fraction (LVEF) <50% were included. Of the 31 patients, 8 received additional catheter ablation with an electrophysiologic study within 3 months after TTA. The rhythm outcome was obtained by 12-lead electrocardiography or 24-hour Holter monitoring.ResultsThe patient cohort had a mean age of 54.9 ± 9.0 years and consisted of 51.6% with persistent AF (n = 16), 45.2% with long-standing persistent AF (n = 14), and 3.2% with paroxysmal AF (n = 1). No patients died during the follow-up period. Compared with baseline, mean postoperative LVEF at 3 months (interquartile range [IQR], 2-6 months) increased significantly (from 39.7 ± 6.1% to 53.6 ± 9.3%; P < .001). At 25 months (IQR, 14-45 months), LVEF was sustained or further improved (from 39.7 ± 6.1% to 58.1 ± 7.5%; P < .001). The rate of sinus rhythm state was 93.5% (29 of 31), and freedom from arrhythmias off AADs after the final procedure was 61.3% (19 of 31) at a median follow-up of 32 months (IQR, 24-54 months).ConclusionsTTA is a safe and effective procedure that improves LV function and restores sinus rhythm in AF patients with LV dysfunction.
Project description:BackgroundLeft atrial (LA) function can be impaired by the atrial fibrillation (AF) ablation and might be associated with the risk of recurrence. We sought to determine whether the post-procedural changes in LA function impact the risk of recurrence following AF ablation.MethodsWe retrospectively reviewed patients who underwent AF ablation between 2009 and 2011 and underwent transthoracic echocardiography before ablation, 1-day and 3-month after ablation. Peak left atrial contraction strain (PACS) and left atrial emptying fraction (LAEF) were evaluated during sinus rhythm and compared across the three time points. The primary endpoint was atrial tachyarrhythmia recurrence after ablation.ResultsA total of 144 patients were enrolled (mean age 61 ± 11 years, 77% male, 46% persistent AF). PACS and LAEF initially decreased 1-day following ablation but partially recovered within 3 months in PAF patients, with a similar trend in the PerAF patients. After median 24 months follow-up, 68 (47%) patients had recurrence. Patients with recurrence had higher PACS1-day than that in non-recurrence subjects (-10.9 ± 5.0% vs. -13.4 ± 4.7%, p = 0.003). PACS1-day -12% distinguished recurrence cases with a sensitivity of 67.7% and specificity of 60.5%. The Kaplan-Meier curves showed significant difference in 5-year cumulative probability of recurrence between those with PACS ≥ -12% and PACS < -12% (log rank p < 0.0001). Multivariate regression showed that PACS1-day was an independent risk factor of arrhythmia recurrence.ConclusionsLeft atrial function deteriorates immediately following AF ablation and partially recovers in 3 months but remains abnormal in the majority of patients. PACS1-day post procedure predicts arrhythmia recurrence at long-term follow-up.
Project description:Bisphosphonates, including ibandronate, are used in the prevention and treatment of osteoporosis.We report a case of suspected ibandronate-associated arrhythmia, following a single dose of ibandronate in a 55-year-old female. ECG at presentation revealed frequent ectopy and QT/QTc interval prolongation; at follow-up 9 months later the QT/QTc intervals were normalized. Proarrhythmic potential of ibandronate was assessed with a combination of in vivo and in vitro approaches in canines and canine ventricular myocytes. We observed late onset in vivo repolarization instability after ibandronate treatment. Myocytes superfused with ibandronate exhibited action potential duration (APD) prolongation and variability, increased early afterdepolarizations (EADs) and reduced Ito (P < 0.05), with no change in IKr . Ibandronate-induced APD changes and EADs were prevented by inhibition of intracellular calcium cycling. Ibandronate increased sarcoplasmic reticulum calcium load; during washout there was an increase in calcium spark frequency and spontaneous calcium waves. Computational modeling was used to examine the observed effects of ibandronate. While reductions in Ito alone had modest effects on APD, when combined with altered RyR inactivation kinetics, the model predicted effects on APD and SR Ca(2+) load consistent with observed experimental results.Ibandronate may increase the susceptibility to ventricular ectopy and arrhythmias. Collectively these data suggest that reduced Ito combined with abnormal RyR calcium handling may result in a previously unrecognized form of drug-induced proarrhythmia.
Project description:Purpose of reviewTo discuss the role of catheter ablation in treating life-threatening ventricular arrhythmias associated with Brugada syndrome (BrS), by presenting recent findings of BrS arrhythmogenic substrate, mechanisms underlying ventricular arrhythmias, and how they can be treated with catheter ablation.Recent findingsAlmost three decades ago when the clinical entity of Brugada syndrome (BrS) was described in patients who had abnormal coved-type ST elevation in the right precordial EKG leads in patients who had no apparent structural heart disease but died suddenly from ventricular fibrillation. Since its description, the syndrome has galvanized explosive research in this field over the past decades, driving major progress toward better understanding of BrS, gaining knowledge of the genetic pathophysiology and risk stratification of BrS, and creating significant advances in therapeutic modalities. One of such advances is the ability for electrophysiologists to map and identify the arrhythmogenic substrate sites of BrS, which serve as good target sites for catheter ablation. Subsequently, several studies have shown that catheter ablation of these substrates normalizes the Brugada ECG pattern and is very effective in eliminating these substrates and preventing recurrent VF episodes. Catheter ablation has become an important addition for treatment of symptomatic BrS patients with recurrent VT/VF episodes.