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Importance The Implantable Neurostimulator for the Treatment of Parkinson’s Disease (INTREPID) trial was a randomized, double-blind, sham-controlled study of subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of Parkinson disease (PD). Objective To evaluate the long-term (5-year) outcomes and safety of STN-DBS for PD. Design, Setting, and Participants This was a prospective, randomized (3:1), 12-week double-blind sham-controlled study at 23 movement disorder centers across the US with an open-label 5-year follow-up. Patients were implanted and followed up with the Vercise DBS system from May 2013 to December 2022. Eligibility required diagnosis of bilateral idiopathic PD with more than 5 years of motor symptoms, more than 6 hours per day of poor motor function, modified Hoehn and Yahr Scale scores higher than 2, Unified Parkinson’s Disease Rating Scale (UPDRS-III) score of 30 or higher (medication-off state), and 33% or higher improvement in UPDRS-III medication-on score. Intervention Bilateral STN-DBS for moderate to advanced PD. Main Outcomes and Measures Primary outcomes included changes in UPDRS and dyskinesia scores, quality-of-life measures, and safety assessments. Exploratory analyses included medication reduction and DBS association with motor signs. Results A total of 313 patients were enrolled with 191 receiving the DBS system, and 137 participants (72%) completed the study. The study population had a mean (SD) age of 60 (7.9) years, with 139 (73%) male participants. Motor function without medication as measured by UPDRS-III improved from a mean (SD) of 42.8 (9.4) to 21.1 (10.6) at year 1 (51%; 95% CI, 49%-53%; P < .001) and 27.6 (11.6) at year 5 (36%; 95% CI, 33%-38%; P < .001). Activities of daily living without medication as measured by UPDRS-II improved from a mean (SD) of 20.6 (6.0) to 12.4 (6.1) at year 1 (41%; 95% CI, 38%-42%; P < .001) and 16.4 (6.5) at year 5 (22%; 95% CI, 18%-23%; P < .001). Dyskinesia scores decreased from 4.0 (5.1) to 1.0 (2.1) at year 1 (75%; 95% CI, 73%-75%; P < .001) and to 1.2 (2.1) at year 5 (70%; 95% CI, 63%-75%; P < .001). The levodopa equivalent dose was reduced by 28% at year 1, remaining stable at year 5 (28%; 95% CI, 26%-31%; P < .001). The most common serious adverse event was infection (9 participants). Ten deaths were reported, none related to the study. Conclusions and Relevance Although STN-DBS outcomes declined slightly, possibly due to the progressive nature of the disease, patients with PD sustained significant improvement in motor and activities of daily living scores, along with a stable reduction in anti-parkinsonian medication over the 5-year follow-up period.

Background: Ventricular tachycardia (VT) is a life-threatening arrhythmia frequently observed in structural heart diseases, including LMNA-related cardiomyopathy, a genetic disorder associated with high risk of sudden cardiac death and progressive systolic dysfunction. While catheter ablation is an established therapeutic option for VT, its efficacy in cardiac laminopathy remains poorly defined. Objectives: To synthesize available evidence on the role and outcomes of VT ablation in patients with cardiac laminopathy. Methods: A systematic review and single-arm meta-analysis was performed in accordance with PRISMA guidelines. PubMed, Embase, and Cochrane databases were searched for studies reporting VT ablation outcomes in LMNA-related cardiomyopathy. An inverse variance random-effects model was applied for meta-analysis of proportions. Results: Seven studies (six cohorts, one abstract) comprising 62 patients (mean age 53.2 ± 9.7 years; 85% male; 88% with implantable cardioverter-defibrillator) were included. An endocardial/endo-epicardial approach was used in 93% of cases. Acute procedural success was achieved in 37% (95% CI: 14–63%; I 2 = 27.4%), and 28% required multiple procedures. Over a median follow-up of 26 (9–35) months, VT recurrence occurred in 91% (95% CI: 76–100%; I 2 = 37.2%). All-cause mortality was 54% (95% CI: 39–70%; I 2 = 28%), predominantly from cardiac causes (51%, 95% CI: 25–76%; I 2 = 53%), and 14% (95% CI: 1–34%; I 2 = 42%) underwent heart transplantation. Conclusions: In LMNA-related cardiomyopathy, catheter ablation is associated with high VT recurrence, limited long-term success, and substantial cardiovascular mortality and transplantation rates, underscoring the importance of ICD implantation and the need for alternative strategies, including variant-specific and molecularly targeted therapies.

ABSTRACT Introduction Lead‐related venous obstruction is a significant complication of chronic indwelling transvenous leads, which poses unique challenges during cardiac device upgrades. Background The anatomical sequelae of venous occlusion are variable and carry important procedural implications. Occlusions can develop in any part of the venous system, but they most often occur in the subclavian and innominate veins, while the superior vena cava is less frequently affected. Methods In this review, we describe approaches to lead‐related venous occlusion providing step‐by‐step procedural guidance. Results Venoplasty, neovascular channel creation are two main techniques for addressing lead‐related venous obstruction. Conclusion Venoplasty in the setting of an indwelling pacemaker or defibrillator leads can be performed safely and effectively. The difficulty of the procedure lies in crossing the obstruction. Familiarity with various tools is needed for a successful outcome.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45–1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28–2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35–5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53–20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18–0.88]; P interaction =0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

BACKGROUND: Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. METHODS: This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression. RESULTS: In all, 4023 patients (mean age was 47.4 years; 44.5% were women) were included. By day 180, subsequent ischemic stroke occurred in 5.3% of the cohort. In adjusted Cox regression, factors associated with increased risk of subsequent ischemic stroke were prior history of ischemic stroke (adjusted hazard ratio [aHR], 7.31 [95% CI, 1.61–33.13]; P =0.010), presentation within 7 days from first symptoms (aHR, 3.04 [95% CI, 1.04–8.91]; P =0.043), infarct on baseline imaging (aHR, 9.85 [95% CI, 3.65–26.58]; P <0.001), and occlusive dissection (aHR, 2.34 [95% CI, 1.03–5.34]; P =0.043). Only patients with occlusive dissection demonstrated a reduced risk of subsequent ischemic stroke when treated with anticoagulation versus antiplatelets (aHR, 0.36 [95% CI, 0.16–0.80]; P =0.01). CONCLUSIONS: In this post hoc analysis of the STOP-CAD study, several factors associated with subsequent ischemic stroke were identified among patients with CAD. Furthermore, we identified a potential benefit of anticoagulation in patients with CAD with occlusive dissection. These findings require validation by meta-analyses of prior studies to formulate optimal treatment strategies for specific high-risk CAD subgroups.

Background: Transthyretin cardiac amyloidosis (ATTR-CA) carries an elevated risk of developing ventricular arrhythmias (VA) but there remains limited evidence supporting the role of catheter ablation in this population. Purpose: To assess the safety and efficacy of catheter ablation for VA in ATTR-CA. Methods: An electronic database was used to identify all patients suspected of having ATTR-CA who underwent catheter ablation for VA at our institution between January 2010 and December 2023. Patients who did not meet the diagnosis of ATTR-CA and had a negative workup who underwent catheter ablation for ventricular tachycardia (VT) or premature ventricular contractions (PVCs) were used to form a control group matched for age, sex and left ventricular ejection fraction at a ratio of 2:1. Results: 20 controls and 10 cases of ATTR-CA were identified. Examining the two groups at baseline (Table 1), the mean age at index ablation was 67.7±7.0 and 68.6±8.1 years (p=0.359), mean follow-up time was 4.1±3.1 and 4.2±2.6 years (p=0.494), and the proportion of males was 100% and 90% respectively. The ATTR-CA group had a significantly higher proportion of chronic kidney disease (90% vs. 50%, p=0.032) and prior stroke or thrombotic events compared to the control group (50% vs. 10%, p=0.026) with similar CHA 2 DS 2 VASc scores (4.2±1.6 vs. 3.8±1.3, p=0.233). Both groups had comparable left ventricular ejection fraction (41.4%±14% vs. 46.9%±15.2%, p=0.173), VT/PVCs at presentation (40%/60% vs. 25%/75%, p=0.77), use of antiarrhythmics (70% vs. 60%, p=0.592), and high proportion of atrial fibrillation/flutter (70% vs. 90%, p=0.168). Procedural (261.2±101.2 vs. 265.7±125.6 mins, p=0.449) and total energy delivery time (1442.9±1509.1 vs. 1744.6±956.2 secs, p=0.296) was not significantly different in the two groups. Both groups had a significant decrease in PVC burden postablation with a reduction from 26.8% to 3.8% (p=0.024) and from 27.1% to 13.6% (p=0.028) in the ATTR-CA and control group respectively. A downward trend was seen in antitachycardia pacing events for VT postablation in the ATTR-CA (14.7±9.8 vs. 5.3±6.7, p =0.184) and control (193±387.6 vs. 0.67±1.2. p=0.139) groups. No major complications occurred after ablation (Table 2). Mean time to recurrence post-index ablation was similar between both groups (1620.4±483.8 vs. 1498.8±291.4 days, p=0.987, Figure 1). Conclusions: Catheter ablation appears to be safe and effective for VT and PVCs in patients with ATTR-CA.

Abstract Background The right ventricular moderator band-papillary muscle (RV MB-PM) complex has a rich subendocardial network of purkinje fibers which can lead to ventricular arrhythmias (VA)1. Catheter ablation of such arrhythmias is procedurally challenging and there remains limited studies on long-term procedural success. Purpose We aimed to systematically study RV MB-PM complex VA. Methods A single center retrospective study from January 2013 to December 2023 identified 3249 patients who underwent VA ablation. The RV MB-PM complex was targeted in 47 patients. Acute success was defined as suppression of the targeted VA &gt;=30 minutes post ablation. Long-term success was defined as the absence of symptoms, total PVC burden &lt;5% or improvement in EF in patients presenting with isolated PVCs and as freedom from appropriate ICD therapy in patients presenting with malignant PVCs inducing VF, sustained VT or VT storm. Results Mean age was 51.9 ± 16.7 years and 64% were male. 40 (85%) patients had VA targeted from the MB and 7 (15%) from the PM complex (2 anterior, 2 inferior and 3 septal PM). 34 (72%) had no underlying structural heart disease, 3 (6%) ischemic cardiomyopathy and 10 (21%) non-ischemic cardiomyopathy. No patient had delayed gadolinium enhancement in the RV MB-PM complex. VA were inducible in 42 (89%) of patients and activation mapping was used in 9 (19%), pace mapping in 5 (11%) and a combination of activation and pace mapping used in 33 (70%) patients. Intracardiac echocardiography was used in all cases. Pre-QRS duration was 34.0 ± 10.4 ms. Radiofrequency ablation was used in 37 (78.7%) cases, cryotherapy in 4 (8.51%) cases and a combination of the 2 energy sources in 6 (12.8%) cases. In all cases, acute peri-procedural success was achieved. 24 (51.1%) patients presented with isolated PVCs and were followed up for 4.72 ± 3.55 years after their index procedure. 3 patients underwent repeat catheter ablation targeting the same PVC focus but all patients had long term success with a PVC burden of 16.1 ± 12.5% prior to ablation and 2.40 ± 2.44% at last follow-up. 16 patients underwent ablation for recurrent ICD shocks after initially presenting with PVC induced VF. Patients were followed up for 3.22 ± 2.09 years and 14 (88%) patients remained free from ICD therapy. 7 patients had MB ablation for sustained VT and were followed up for 4.06 ± 3.77 years. 5 (71%) patients remained free from ICD therapy. A purkinje potential was seen in 8% (2/24) cases of isolated PVCs and in 39% (9/23) cases of PVC induced VF or VT (p=0.13). Conclusions RV MB-PM VA commonly present with malignant VF and a purkinje potential is more likely to be seen in these cases suggesting different VA mechanisms to isolated PVCs and catheter ablation is an effective long-term strategy.

Abstract Aims Radiation therapy (RT) is an integral component of cancer therapy but associated with adverse events. Our goal was to establish risk prediction models for major adverse cardiovascular and cerebrovascular events (MACCE) after chest RT. Methods and results A retrospective study of lung/breast cancer patients who had chest RT with planning CT at Mayo Clinic between 01/2010 and 01/2014. Predictive models were developed based on weighted independent predictors using a derivation (406 lung and 711 breast cancer) and validation cohort (179 lung and 234 breast cancer). Patient characteristics, pre-RT CT for coronary artery calcification (CAC), and post-RT MACCE data were reviewed. Post-RT MACCE occurred in 6.1 and 5.6% in the derivation and validation cohort over a mean follow-up of 42 ± 13 months. Post-therapy model (C2AD2) included CAC (two points), MACCE history (two points), age ≥74 (three points), DM (two points), and mean heart radiation dose ≥ 850 mGy (two points), and pre-therapy model (C2AD) included post-therapy model parameters minus mean heart radiation dose. Both models stratified patients into three risk groups: low (0–2), intermediate (3–5), and high (≥6). Post-RT MACCE across these groups were 2.7, 8.9, and 19.8% in the derivation, and 3.9, 6.6, and 16.4% in the validation cohort for post-therapy model (C2AD2) and 2.8, 9.2, and 20.4% in the derivation and 3.7, 9.2, and 13.2% in the validation cohort for pre-therapy model. Both models showed statistically significant graded survival outcome. Conclusion Post-therapy (C2AD2) and pre-therapy (C2AD) models are simple, easy to use and effective tools to stratify breast and lung cancer patients undergoing chest radiation for post-RT MACCE.