Dofetilide for the treatment of premature ventricular complexes and ventricular tachycardia in patients with structural heart disease.

BACKGROUND: Dofetilide is a class III antiarrhythmic agent approved for the treatment of atrial fibrillation and atrial flutter. Given the efficacy of other class III agents, it has been used off-label for the treatment of premature ventricular complexes (PVCs) and ventricular tachycardias (VTs). OBJECTIVE: The purpose of this study was to determine the efficacy and safety of dofetilide for ventricular arrythmias (VAs). METHODS: In this retrospective cohort study, 81 patients (59 men; age = 60 ± 14 years; LVEF = 0.34 ± 0.16) were admitted for dofetilide initiation to treat PVCs (29), VTs (42) or both (10). A ≥ 80% decrease in PVC burden was defined as a satisfactory response. An ICD was present in 72 patients (89%). Another antiarrhythmic was previously used in 50 patients (62%). Prior catheter ablation had been performed in 33 patients (41%). RESULTS: During intitiation, dofetilide was discontinued in 12 patients (15%) due to QT prolongation (8) and inefficacy to suppress VAs (4). Among the 32 patients with PVCs who successfully started dofetilide, the mean PVC burden decreased from 20 ± 10% to 8 ± 8% at a median follow-up of 2.6 months (p < .001). PVC burden was reduced by ≥80% in only 11/32 patients (34%). During 7 ± 1 years of follow-up, 41/69 patients (59%) continued to have VAs and received appropriate ICD therapies for monomorphic VTs (35) and polymorphic VT/VF (6) at a median of 8.0 (IQR 2.6-33.2) months. Dofetilide had to be discontinued in 50/69 patients (72%) due to inefficacy or intolerance. The composite outcome of VT/VF recurrence, heart transplantation, or death occurred in 6/12 patients (50%) without dofetilide and 49/69 patients (71%) with dofetilide. The event free survival was similar between patients treated with and without dofetilide (log-rank p = .55). CONCLUSIONS: Treatment with dofetilide was associated with a decrease in PVCs, however clinically significant suppression occurred in a minority of patients. Dofetilide failed to suppress the occurrence of VTs in a majority of patients.

Substrate Characterization and Outcomes of Ventricular Tachycardia Ablation in Amyloid Cardiomyopathy: A Multicenter Study.

BACKGROUND: Sustained ventricular tachycardia (VT) in cardiac amyloidosis is uncommon, and the substrate and outcomes of catheter ablation are not defined. METHODS: We included 22 consecutive patients (mean age, 68±10 years; male sex, 91%) with cardiac amyloidosis (ATTR [transthyretin], n=16; light chain, n=6) undergoing catheter ablation for VT/ventricular fibrillation (VF) between 2013 and 2023 in a retrospective, observational, international study. The primary efficacy outcome was recurrent VT/VF during follow-up, while the primary safety end point included major procedure-related adverse events. RESULTS: The indication for ablation was drug-refractory VT in 17 patients (77%), and premature ventricular complex-initiated polymorphic VT/VF in 5 patients (23%). Catheter ablation was performed using endocardial (n=17.77%) or endo-epicardial approaches (n=5.23%). Complete endocardial electroanatomical voltage maps of the left and right ventricles were obtained in 17 (77%) and 10 (45%) patients, respectively. Each patient had evidence of low-voltage areas, most commonly involving the interventricular septum (n=16); late potentials were recorded in 16 patients (73%). A median of 1 (1-2) VT was inducible per patient; 12 of the 26 mappable VTs (46%) originated from the interventricular septum. Complete procedural success was achieved in 16 patients (73%), with 4 (18%) major procedure-related adverse events. After a median follow-up of 32 (14-42) months, sustained VT/VF recurrence was observed in 9 patients (41%); survival free from VT/VF recurrence was 56% (95% CI, 36%-86%) at 36-month follow-up, and most patients remained on antiarrhythmic drugs. A significant reduction in per patient implantable cardioverter defibrillator therapies was noted in the 6-month period after ablation (before: 6 [4-9] versus after: 0 [0-0]; P<0.001). In multivariable analysis, complete procedural success was associated with reduced risk of recurrent VT/VF (hazard ratio, 0.002; P=0.034). CONCLUSIONS: Catheter ablation can achieve control of recurrent VT/VF in more than half of patients with cardiac amyloidosis, and the reduction in VT/VF burden post-ablation may be relevant for quality of life. Septal substrate and risk of procedure-related complications challenge successful management of patients with cardiac amyloidosis and VT/VF.

Quinidine for ventricular arrhythmias: A comprehensive review.

Quinidine, the first antiarrhythmic drug, was widely used during the 20th century. Multiple studies have been conducted to provide insights into the pharmacokinetics and pleiotropic effects of Class Ia antiarrhythmic drugs. However, safety concerns and the emergence of new drugs led to a decline in their use during the 1990s. Despite this, recent studies have reignited the interest in quinidine, particularly for ventricular arrhythmias, where other antiarrhythmics have failed. In conditions such as Brugada syndrome, idiopathic ventricular fibrillation, early repolarization syndrome, short QT syndrome, and electrical storms, quinidine remains a valuable asset. Starting from the European and American recommendations, this comprehensive review aimed to explore the various indications for quinidine and the studies that support its use. We also discuss the potential future of quinidine, including the necessary research to optimize its use and patient selection. Additionally, it addresses the imperative task of mitigating the iatrogenic burden associated with quinidine usage and confronts the challenge of ensuring drug accessibility.

Catheter ablation of parahisian premature ventricular complexes in patients with and without cardiac scar.

BACKGROUND: Ablation of premature ventricular complexes (PVCs) originating from the parahisian area is challenging. Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) scar may influence procedural outcomes; the impact of cardiac scar on parahisian PVCs has not been described. OBJECTIVE: The objective of this study was to examine the incidence and significance of LGE-CMR scarring in patients undergoing ablation for parahisian PVCs. METHODS: Consecutive patients who underwent preprocedure LGE-CMR imaging and ablation of parahisian PVCs were included. Acute and long-term outcomes were examined. RESULTS: Forty-eight patients were included (male, n = 37; age, 66 ± 10 years; ejection fraction, 50% ± 12%; preprocedure PVC burden, 21% ± 12%). Intramural LGE-CMR scar was present in 33 of 48 (69%) patients. Cryoablation was used in 9 patients; ablation in multiple chambers was required in 28 (58%) patients. The PVC site of origin (SOO) was intramural (n = 25 patients), left ventricular (n = 5), and right ventricular (n = 18). Patients with LGE-CMR scar were more likely to have intramural PVCs (64% vs 27%; P < .04) and to require ablation in multiple cardiac chambers (58% vs 13%; P < .02). Patients with intramural scar required longer duration of ablation delivery (31 ± 20 minutes vs 17 ± 8 minutes; P < .02). Acute procedural success was 69%; PVC burden on follow-up was 6% ± 9% and similar for those with and without scar. CONCLUSION: Ablation of parahisian PVCs often requires mapping and ablation of multiple cardiac chambers, with an intramural SOO identified in most patients. An intramural scar was associated with an intramural SOO of the PVCs requiring more extensive ablation procedures, with similar long-term outcomes compared with those without scar.

Ventricular arrhythmias in patients with bicuspid aortic valves.

INTRODUCTION: Bicuspid aortic valves (BAV) are the most common congenital heart defects and the extent of ventricular arrhythmias (VA) in patients with BAV is unclear. The objective of this study is to describe VAs and late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) in patients with BAV. METHODS: A total of 19 patients with BAV (18 males, age: 58 ± 13 years) were referred for VA ablation procedures. Ten patients had BAVs at the time of ablation, nine patients had prior aortic valve replacement for a BAV. All but one patient had LGE-CMR and all patients underwent programmed ventricular stimulation at the time of the ablation. RESULTS: Frequent PVCs were the targeted VAs in 17/19 patients and VT in 2/19 patients. Monomorphic ventricular tachycardia (VT) was inducible in 6 patients. A total of 15 VTs were inducible (2.5 ± 1.0 VTs per patient with a mean cycle length of 322 ± 83 msec). LGE was present in 13 patients. Patients with inducible VT had larger borderzone and core scar compared to non-inducible patients (7.8 ± 2.1 cm3 vs. 2.5 ± 3.1 cm3 and 5.1 ± 2.6 cm3 vs. 1.9 ± 3.0 cm3, p-value < .05 for both). PVCs and VTs were mapped to the periaortic valve area in 12 patients and 4 patients, respectively. The PVC burden was reduced from 27 ± 13 to 3 ± 6 (p < .001) and the ejection fraction improved from 49 ± 13% to 55 ± 9% (p = .005). CONCLUSIONS: VAs in patients with BAV often originate from the perivalvular area and patients often have LGE and inducible VT. LGE may be due to ventricular remodeling secondary to the presence of BAV and harbors the arrhythmogenic substrate for VT.

Clinical outcomes of patients referred for left atrial appendage exclusion who did and did not undergo the procedure.

BACKGROUND: Left atrial appendage exclusion (LAAE) is an effective alternative to long-term anticoagulation in patients with atrial fibrillation. Not all patients considered for LAAE undergo the procedure because of ineligibility, anatomic or medical constraints, and preference of the patient. OBJECTIVE: The objective of this study was to report on the management strategies and long-term clinical outcomes of patients referred to a dedicated multidisciplinary LAAE clinic, including all who subsequently did and did not undergo LAAE. METHODS: This was a retrospective analysis of prospectively acquired data from all patients referred to the comprehensive multidisciplinary LAAE clinic at the University of Michigan between 2016 and 2022. A consecutive 301 patients (age, 75 ± 8 years; 106 women) with atrial fibrillation were evaluated. LAAE was performed in 168 patients (56%) with use of the Watchman device in 146 (49%) and surgically in 22 (7%). LAAE was not performed in 133 patients (44%, no-LAAE group) because of ineligibility in 62 (21%), anatomic constraints in 23 (7%), and preference of the patient in 48 (36%). The CHA2DS2-VASc score (4.7 ± 1.5 vs 4.1 ± 1.6; P = .002) and HAS-BLED score (3.4 ± 1.0 vs 2.8 ± 1.1; P < .001) were higher in the LAAE groups. RESULTS: Anticoagulant therapy was discontinued in 137 of 146 (94%) and 61 of 133 (61%) in the Watchman and no-LAAE groups, respectively (P < .001). During a median follow-up of 2.2 years (interquartile range, 1.2-4.0 years), in the LAAE (n = 168) and no-LAAE (n = 133) groups, respectively, 39 (23%) vs 29 (22%) deaths, 13 (8%) vs 5 (4%) thromboembolic events, and 24 (14%) vs 23 (17%) bleeding complications occurred. Continued long-term anticoagulation was not a predictor of clinical outcomes. CONCLUSION: After a comprehensive evaluation in a multidisciplinary clinic, ∼50% of the patients referred for LAAE did not proceed with LAAE and resumed anticoagulation.

Posterior left atrial isolation is associated with a lower incidence of atrial tachycardia in patients with persistent atrial fibrillation.

BACKGROUND: Patients may develop atrial tachycardia (AT) after left atrial (LA) ablation of persistent atrial fibrillation (AF). METHODS: The population consisted of 101 consecutive patients (age = 64.3 ± 8.7 years, 70 males (69%), LA = 4.6 ± 0.8 cm, ejection fraction = 48.5 ± 16%) undergoing their initial procedure for persistent AF. After pulmonary vein isolation, patients either underwent posterior LA isolation (n = 50; study group) or linear ablation at the LA roof with verification of conduction block (n = 51; control group). RESULTS: A repeat procedure was performed in 17 (34%) and 28 (55%) patients in the study and control groups, respectively (p = 0.02). Patients in the study group were less likely to develop AT (9/50 [18%] vs. 18/51 [35%]; p = 0.02), roof-dependent (1/50 [2%] vs. 8/51 [16%]; p = 0.008), and multi-loop AT (6/50 [12%] vs. 14/51 [27%]; p = 0.03) as compared to controls. Among various factors, only posterior LA isolation was associated with a lower likelihood of AT recurrence and roof tachycardia at redo procedure (OR, 0.37; 95% CI, 0.1 to 1.00, p = 0.05, and OR, 0.1, 95% CI, 0.01 to 0.96; p < 0.05, respectively). CONCLUSIONS: In patients with persistent AF, posterior LA isolation is associated with a lower risk of a redo procedure, roof-dependent macro-reentry, and post-ablation AT in general as compared to controls who only received roof ablation. Posterior LA isolation also obviates the need for pacing maneuvers, and may be a more definitive endpoint than linear ablation at the LA roof.

Surpoint algorithm for improved guidance of ablation for ventricular tachycardia (SURFIRE-VT): A pilot study.

INTRODUCTION: The utility of ablation index (AI) to guide ventricular tachycardia (VT) ablation in patients with structural heart disease is unknown. The aim of this study was to assess procedural characteristics and clinical outcomes achieved using AI-guided strategy (target value 550) or conventional non-AI-guided parameters in patients undergoing scar-related VT ablation. METHODS: Consecutive patients (n = 103) undergoing initial VT ablation at a single center from 2017 to 2022 were evaluated. Patient groups were 1:1 propensity-matched for baseline characteristics. Single lesion characteristics for all 4707 lesions in the matched cohort (n = 74) were analyzed. The impact of ablation characteristics was assessed by linear regression and clinical outcomes were evaluated by Cox proportional hazard model. RESULTS: After propensity-matching, baseline characteristics were well-balanced between AI (n = 37) and non-AI (n = 37) groups. Lesion sets were similar (scar homogenization [41% vs. 27%; p = .34], scar dechanneling [19% vs. 8%; p = .18], core isolation [5% vs. 11%; p = .4], linear and elimination late potentials/local abnormal ventricular activities [35% vs. 44%; p = .48], epicardial mapping/ablation [11% vs. 14%; p = .73]). AI-guided strategy had 21% lower procedure duration (-47.27 min, 95% confidence interval [CI] [-81.613, -12.928]; p = .008), 49% lower radiofrequency time per lesion (-13.707 s, 95% CI [-17.86, -9.555]; p < .001), 21% lower volume of fluid administered (1664 cc [1127, 2209] vs. 2126 cc [1750, 2593]; p = .005). Total radiofrequency duration (-339 s [-24%], 95%CI [-776, 62]; p = .09) and steam pops (-155.6%, 95% CI [19.8%, -330.9%]; p = .08) were nonsignificantly lower in the AI group. Acute procedural success (95% vs. 89%; p = .7) and VT recurrence (0.97, 95% CI [0.42-2.2]; p = .93) were similar for both groups. Lesion analysis (n = 4707) demonstrated a plateau in the magnitude of impedance drops once reaching an AI of 550-600. CONCLUSION: In this pilot study, an AI-guided ablation strategy for scar-related VT resulted in shorter procedure time and average radiofrequency time per lesion with similar acute procedural and intermediate-term clinical outcomes to a non-AI-guided approach utilizing traditional ablation parameters.

Ventricular Tachycardia Ablation in Patients With Desmoplakin Cardiomyopathy.

BACKGROUND: Desmoplakin (DSP) pathogenic variants are rare causes of arrhythmogenic cardiomyopathy and often involve the right and left ventricles. Ventricular tachycardia (VT) ablations may be required in these patients, but procedural characteristics have not been reported. OBJECTIVES: In this study, the authors sought to report a multicenter experience of VT ablation in patients with DSP pathogenic variants. METHODS: VT ablations performed in patients with known DSP pathogenic variants were analyzed across 6 centers in 3 countries. Patient characteristics and acute and long-term procedural outcomes were reported. RESULTS: A total of 20 patients (13 men, median age 43 years [Q1-Q3: 41.5-53.0 years], left ventricular ejection fraction 43.0% [Q1-Q3: 41.5%-53.0%], 11 previous failed ablations) were referred for VT ablation procedures. All patients had symptomatic VTs, with ICD therapy in 19 patients. Epicardial procedures were performed in 16 of the 20 patients. VT target sites were located in the right ventricular (RV) endocardium (n = 11), the RV epicardium (n = 4), the left ventricular (LV) endocardium (n = 2) and the LV epicardium (n = 7). In 3 patients, the VT target sites were in close proximity to coronary arteries, limiting ablation. During follow-up, VTs recurred in 11 patients, and repeated ablations were performed in 9 patients. Allowing for multiple procedures, 19 of the 20 patients remained free of VT recurrence after a median follow-up of 18 months [Q1-Q3: 5-60 months]. CONCLUSIONS: Patients with DSP cardiomyopathy often have biventricular involvement, and ablation procedures often require ablation in both ventricles and the epicardium. Recurrences are not uncommon, and the pathologic substrate can be located in close proximity to epicardial coronary arteries, limiting the success rate of ablations.

Pleomorphism of premature ventricular complexes originating from papillary muscles and their myocardial connections.

BACKGROUND: Patients with arrhythmias originating from papillary muscles (PAPs) often have pleomorphic ventricular arrhythmias (PVAs) that can result in failed ablations. The mechanism of PVAs is unknown. OBJECTIVE: The purpose of this study was to assess the prevalence and mechanisms of PVAs and the impact on outcomes in patients with focal left ventricular PAP ventricular arrhythmias (VAs). METHODS: The sites of origin (SOOs) of VAs in 43 consecutive patients referred for ablation of focal left ventricular PAP VAs were determined by activation and pacemapping. SOOs were classified as (1) unifocal generating a single VA morphology; (2) unifocal from a deeper-seated origin generating multiple VA morphologies; (3) unifocal located on a PAP branching site; (4) multifocal from a single or multiple PAPs generating multiple VA morphologies; and (5) multifocal from a PAP and a different anatomic source. RESULTS: Most patients had multiple morphologies (n = 34 [79%]) and multiple mechanisms (79%) generating the different VA morphologies. Most of the patients with PVAs had multiple SOOs from a single or different PAPs (n = 23 [68%]), followed by patients with SOOs from PAP and non-PAP sites (n = 19 [56%]). In 13 patients (38%), single SOOs accounted for the observed PVAs. The frequent observation (n = 20) of changing QRS morphologies after radiofrequency energy delivery targeting a single VA suggests the presence of a deeper focus with changing sites of preferential conduction. CONCLUSION: VA pleomorphism in patients with PAP arrhythmias is most often due to premature ventricular complexes originating from different SOOs. The second most common cause is preferential conduction from a single SOO via PAP branching sites.