Recurrence After Atrial Fibrillation Ablation and Investigational Biomarkers of Cardiac Remodeling.

BACKGROUND: Recurrence after atrial fibrillation (AF) ablation remains common. We evaluated the association between recurrence and levels of biomarkers of cardiac remodeling, and their ability to improve recurrence prediction when added to a clinical prediction model. METHODS AND RESULTS: Blood samples collected before de novo catheter ablation were analyzed. Levels of bone morphogenetic protein-10, angiopoietin-2, fibroblast growth factor-23, insulin-like growth factor-binding protein-7, myosin-binding protein C3, growth differentiation factor-15, interleukin-6, N-terminal pro-brain natriuretic peptide, and high-sensitivity troponin T were measured. Recurrence was defined as ≥30 seconds of an atrial arrhythmia 3 to 12 months postablation. Multivariable logistic regression was performed using biomarker levels along with clinical covariates: APPLE score (Age >65 years, Persistent AF, imPaired eGFR [<60 ml/min/1.73m2], LA diameter ≥43 mm, EF <50%; which includes age, left atrial diameter, left ventricular ejection fraction, persistent atrial fibrillation, and estimated glomerular filtration rate), preablation rhythm, sex, height, body mass index, presence of an implanted continuous monitor, year of ablation, and additional linear ablation. A total of 1873 participants were included. A multivariable logistic regression showed an association between recurrence and levels of angiopoietin-2 (odds ratio, 1.08 [95% CI, 1.02-1.15], P=0.007) and interleukin-6 (odds ratio, 1.02 [95% CI, 1.003-1.03]; P=0.02). The area under the receiver operating characteristic curve of a model that only contained clinical predictors was 0.711. The addition of any of the 9 studied biomarkers to the predictive model did not result in a statistically significant improvement in the area under the receiver operating characteristic curve. CONCLUSIONS: Higher angiopoietin-2 and interleukin-6 levels were associated with recurrence after atrial fibrillation ablation in multivariable modeling. However, the addition of biomarkers to a clinical prediction model did not significantly improve recurrence prediction.

Persistent and Recurrent Device-Related Thrombus After Left Atrial Appendage Closure: Incidence, Predictors, and Outcomes.

BACKGROUND: Scarce data exist on the evolution of device-related thrombus (DRT) after left atrial appendage closure (LAAC). OBJECTIVES: This study sought to assess the incidence, predictors, and clinical impact of persistent and recurrent DRT in LAAC recipients. METHODS: Data were obtained from an international multicenter registry including 237 patients diagnosed with DRT after LAAC. Of these, 214 patients with a subsequent imaging examination after the initial diagnosis of DRT were included. Unfavorable evolution of DRT was defined as either persisting or recurrent DRT. RESULTS: DRT resolved in 153 (71.5%) cases and persisted in 61 (28.5%) cases. Larger DRT size (OR per 1-mm increase: 1.08; 95% CI: 1.02-1.15; P = 0.009) and female (OR: 2.44; 95% CI: 1.12-5.26; P = 0.02) were independently associated with persistent DRT. After DRT resolution, 82 (53.6%) of 153 patients had repeated device imaging, with 14 (17.1%) cases diagnosed with recurrent DRT. Overall, 75 (35.0%) patients had unfavorable evolution of DRT, and the sole predictor was average thrombus size at initial diagnosis (OR per 1-mm increase: 1.09; 95% CI: 1.03-1.16; P = 0.003), with an optimal cutoff size of 7 mm (OR: 2.51; 95% CI: 1.39-4.52; P = 0.002). Unfavorable evolution of DRT was associated with a higher rate of thromboembolic events compared with resolved DRT (26.7% vs 15.1%; HR: 2.13; 95% CI: 1.15-3.94; P = 0.02). CONCLUSIONS: About one-third of DRT events had an unfavorable evolution (either persisting or recurring), with a larger initial thrombus size (particularly >7 mm) portending an increased risk. Unfavorable evolution of DRT was associated with a 2-fold higher risk of thromboembolic events compared with resolved DRT.

Loperamide Induced Recurrent Torsades de Pointes: A Case Report.

PURPOSE: A case of loperamide-induced recurrent torsades de pointes is reported to raise awareness of an increasingly common phenomenon that could be encountered by medical providers during the current opioid epidemic. SUMMARY: A 40 year-old-man with a prior history of opioid abuse who presented to the emergency department after taking up to 100 tablets of loperamide 2 mg daily for 5 years to blunt opioid withdrawal symptoms and was subsequently admitted to the intensive care unit for altered mental status and hyperthermia. The patient had prolonged QTc and 2 episodes of torsades de pointes (TdP) that resulted in cardiac arrest with return of spontaneous circulation. He was managed with isoproterenol, overdrive pacing, and methylnatrexone with no other events of TdP or cardiac arrest. CONCLUSION: A 40-year-old male who developed torsades de pointes from loperamide overdose effectively treated with overdrive pacing, isoproterenol, and methylnatrexone.

Temporal Changes and Clinical Implications of Delayed Peridevice Leak Following Left Atrial Appendage Closure.

OBJECTIVES: The aim of this study was to assess temporal changes and clinical implications of peridevice leak (PDL) after left atrial appendage closure. BACKGROUND: Endocardial left atrial appendage closure devices are alternatives to long-term oral anticoagulation (OAC) for patients with atrial fibrillation. PDL >5 mm may prohibit discontinuation of OAC. METHODS: Patients included in the study had: 1) successful Watchman device implantation without immediate PDL; 2) new PDL identified at 45 to 90 days using transesophageal echocardiography; 3) eligibility for OAC; and 4) 1 follow-up transesophageal echocardiographic study for PDL surveillance. Relevant clinical and imaging data were collected by chart review. The combined primary outcome included failure to stop OAC after 45 to 90 days, transient ischemic attack or stroke, device-related thrombi, and need for PDL closure. RESULTS: Relevant data were reviewed for 1,039 successful Watchman device implantations. One hundred eight patients (10.5%) met the inclusion criteria. The average PDL at 45 to 90 days was 3.2 ± 1.6 mm. On the basis of a median PDL of 3 mm, patients were separated into ≤3 mm (n = 73) and >3 mm (n = 35) groups. In the ≤3 mm group, PDL regressed significantly (2.2 ± 0.8 mm vs 1.6 ± 1.4 mm; P = 0.002) after 275 ± 125 days. In the >3 mm group, there was no significant change in PDL (4.9 ± 1.4 mm vs 4.0 ± 3.0 mm; P = 0.12) after 208 ± 137 days. The primary outcome occurred more frequently (69% vs 34%; P = 0.002) in the >3 mm group. The incidence of transient ischemic attack or stroke in patients with PDL was significantly higher compared with patients without PDL, irrespective of PDL size. CONCLUSIONS: New PDL detected by transesophageal echocardiography at 45 to 90 days occurred in a significant percentage of patients and was associated with worse clinical outcomes. PDL ≤3 mm tended to regress over time.

Predictors of Device-Related Thrombus Following Percutaneous Left Atrial Appendage Occlusion.

BACKGROUND: Device-related thrombus (DRT) has been considered an Achilles' heel of left atrial appendage occlusion (LAAO). However, data on DRT prediction remain limited. OBJECTIVES: This study constructed a DRT registry via a multicenter collaboration aimed to assess outcomes and predictors of DRT. METHODS: Thirty-seven international centers contributed LAAO cases with and without DRT (device-matched and temporally related to the DRT cases). This study described the management patterns and mid-term outcomes of DRT and assessed patient and procedural predictors of DRT. RESULTS: A total of 711 patients (237 with and 474 without DRT) were included. Follow-up duration was similar in the DRT and no-DRT groups, median 1.8 years (interquartile range: 0.9-3.0 years) versus 1.6 years (interquartile range: 1.0-2.9 years), respectively (P = 0.76). DRTs were detected between days 0 to 45, 45 to 180, 180 to 365, and >365 in 24.9%, 38.8%, 16.0%, and 20.3% of patients. DRT presence was associated with a higher risk of the composite endpoint of death, ischemic stroke, or systemic embolization (HR: 2.37; 95% CI, 1.58-3.56; P < 0.001) driven by ischemic stroke (HR: 3.49; 95% CI: 1.35-9.00; P = 0.01). At last known follow-up, 25.3% of patients had DRT. Discharge medications after LAAO did not have an impact on DRT. Multivariable analysis identified 5 DRT risk factors: hypercoagulability disorder (odds ratio [OR]: 17.50; 95% CI: 3.39-90.45), pericardial effusion (OR: 13.45; 95% CI: 1.46-123.52), renal insufficiency (OR: 4.02; 95% CI: 1.22-13.25), implantation depth >10 mm from the pulmonary vein limbus (OR: 2.41; 95% CI: 1.57-3.69), and non-paroxysmal atrial fibrillation (OR: 1.90; 95% CI: 1.22-2.97). Following conversion to risk factor points, patients with ≥2 risk points for DRT had a 2.1-fold increased risk of DRT compared with those without any risk factors. CONCLUSIONS: DRT after LAAO is associated with ischemic events. Patient- and procedure-specific factors are associated with the risk of DRT and may aid in risk stratification of patients referred for LAAO.

Left atrial appendage closure in patients with prohibitive anatomy: Insights from PINNACLE FLX.

BACKGROUND: Watchman 2.5 (Boston Scientific Inc, Marlborough, MA) implant success approaches 95% in registries, yet many patients are not attempted because of complex left atrial appendage (LAA) anatomy. Watchman FLX can expand the range of ostium width (14-31.5 mm) and depth available for LAA closure. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of Watchman FLX in patients with a failed Watchman 2.5 attempt or prohibitive LAA anatomy. METHODS: The roll-in (n = 58) and primary effectiveness (n = 400) cohorts of the PINNACLE FLX trial comprised the study population. Subjects were identified who previously failed implantation of Watchman 2.5 (n = 11) or were not attempted because of prohibitive LAA anatomy (n = 88). Demographic characteristics, implant procedure details, and TEE follow-up data were compared to controls composed of enrollees not meeting these criteria (n = 359). RESULTS: Watchman FLX LAA closure was successfully implanted in all subjects with a prior failed Watchman 2.5 attempt (n = 11 of 11). Subjects with previously failed Watchman 2.5 were more likely to receive a 35 mm FLX device than controls (27.3% vs 7.3%; P = .047). Patients with prohibitive anatomy had smaller LAA dimensions than did controls (diameter 18.0 ± 4 mm vs 20.4 ± 3 mm; P < .001 and length 23.7 ± 5 mm vs 28.9 ± 5 mm; P < .001). There was no difference in age, sex, CHA2DS2-VASc score, HAS-BLED score, or primary efficacy between cohorts. Transesophageal echocardiography (TEE) at 12 months showed zero leak in 90.9% in the failed Watchman 2.5 cohort, 91.3% in the prohibitive anatomy cohort, and 89.5% in the control cohort (P = .84). Overall and cardiovascular mortality was lower in the prohibitive anatomy cohort (1.2% vs 8.8% in controls; P = .02). CONCLUSION: Watchman FLX implantation in patients with a prior failed Watchman 2.5 attempt or prohibitive LAA anatomy remained safe and highly effective. The association of reduced overall mortality with smaller LAA dimension warrants future study.

Subxiphoid Hybrid Epicardial-Endocardial Atrial Fibrillation Ablation and LAA Ligation: Initial Sub-X Hybrid MAZE Registry Results.

OBJECTIVES: The aim of this study was to assess the safety and efficacy of a new subxiphoid hybrid epicardial-endocardial atrial fibrillation (AF) ablation and left atrial appendage (LAA) ligation approach for the treatment of persistent AF. BACKGROUND: Surgical hybrid ablation procedures have shown promise for maintaining sinus rhythm versus catheter ablation but are associated with increased periprocedural adverse events. METHODS: Patients with symptomatic persistent AF (n = 33, mean age 64 ± 9 years, 25 men) who had antiarrhythmic drug therapy or prior catheter ablation was unsuccessful were referred for hybrid epicardial-endocardial AF ablation and LAA exclusion. LAA closure was confirmed by transesophageal echocardiographic Doppler flow and/or computed tomographic angiography 1 to 3 months post-ligation. The incidence of atrial tachycardia or AF recurrence, LAA closure, thromboembolic events, and post-operative complications were assessed. RESULTS: All 33 patients underwent successful LAA ligation with epicardial ablation of the posterior left atrial wall, as well as endocardial pulmonary vein isolation and cavotricuspid isthmus ablation. Freedom from atrial tachycardia or AF was 91% (20 of 22 patients) at 6 months, 90% (18 of 20 patients) at 12 months, 92% (11 of 12 patients) at 18 months, and 92% (11 of 12) at 24 months. There were no acute periprocedural complications (<7 days). Thirty-day adverse events included 2 patients with pericardial effusion requiring pericardiocentesis and 1 incisional hernia repair. There were no long-term complications, strokes, or deaths. LAA ligation was complete in 27 of 33 subjects (82%), with 6 subjects having leaks of <5 mm. CONCLUSIONS: Subxiphoid hybrid epicardial-endocardial ablation with LAA ligation is feasible, safe, and effective. Future prospective studies are needed to validate these initial findings.

When to Refer Patients for Left Atrial Appendage Closure.

Referring patients with nonvalvular atrial fibrillation (NVAF) for left atrial appendage closure (LAAC) device should be based on bleeding risks, poor anticoagulation compliance, and patient goals. Patient selection should consider overall prognosis and risk of implant procedure. We detail specific clinical scenarios where LAAC could be considered, based on FDA-approved indications. The indications for LAAC are different in Europe. High-risk scenarios in which LAA occlusion may be preferred alone, or in addition to oral anticoagulation use, are reviewed. Ongoing clinical trials and newer device designs will help change the appropriate post-implant drug regimen which will affect patient and device selection.

Inflammatory markers associated with osteoarthritis after destabilization surgery in young mice with and without Receptor for Advanced Glycation End-products (RAGE).

HtrA1, Ddr-2, and Mmp-13 are reliable biomarkers for osteoarthritis (OA), yet the exact mechanism for the upregulation of HtrA-1 is unknown. Some have shown that chondrocyte hypertrophy is associated with early indicators of inflammation including TGF-ß and the Receptor for Advanced Glycation End-products (RAGE). To examine the correlation of inflammation with the expression of biomarkers in OA, we performed right knee destabilization surgery on 4-week-old-wild type and RAGE knock-out (KO) mice. We assayed for HtrA-1, TGF-ß1, Mmp-13, and Ddr-2 in articular cartilage at 3, 7, 14, and 28 days post-surgery by immunohistochemistry on left and right knee joints. RAGE KO and wild type mice both showed staining for key OA biomarkers. However, RAGE KO mice were significantly protected against OA compared to controls. We observed a difference in the total number of chondrocytes and percentage of chondrocytes staining positive for OA biomarkers between RAGE KO and control mice. The percentage of cells staining for OA biomarkers correlated with severity of cartilage degradation. Our results indicate that the absence of RAGE did protect against the development of advanced OA. We conclude that HtrA-1 plays a role in lowering TGF-ß1 expression in the process of making articular cartilage vulnerable to damage associated with OA progression.