ALTERED PROFILES OF EXTRACELLULAR MITOCHONDRIAL DNA IN IMMUNOPARALYZED PEDIATRIC PATIENTS AFTER THERMAL INJURY.

ABSTRACT: Background: Thermal injury is a major cause of morbidity and mortality in the pediatric population worldwide with secondary infection being the most common acute complication. Suppression of innate and adaptive immune function is predictive of infection in pediatric burn patients, but little is known about the mechanisms causing these effects. Circulating mitochondrial DNA (mtDNA), which induces a proinflammatory signal, has been described in multiple disease states but has not been studied in pediatric burn injuries. This study examined the quantity of circulating mtDNA and mtDNA mutations in immunocompetent (IC) and immunoparalyzed (IP) pediatric burn patients. Methods: Circulating DNA was isolated from plasma of pediatric burn patients treated at Nationwide Children's Hospital Burn Center at early (1-3 days) and late (4-7 days) time points postinjury. These patients were categorized as IP or IC based on previously established immune function testing and secondary infection. Three mitochondrial genes, D loop, ND1, and ND4, were quantified by multiplexed qPCR to assess both mtDNA quantity and mutation load. Results: At the early time point, there were no differences in plasma mtDNA quantity; however, IC patients had a progressive increase in mtDNA over time when compared with IP patients (change in ND1 copy number over time 3,880 vs. 87 copies/day, P = 0.0004). Conversely, the IP group had an increase in mtDNA mutation burden over time. Conclusion: IC patients experienced a significant increase in circulating mtDNA quantity over time, demonstrating an association between increased mtDNA release and proinflammatory phenotype in the burn patients. IP patients had significant increases in mtDNA mutation load likely representative of degree of oxidative damage. Together, these data provide further insight into the inflammatory and immunological mechanisms after pediatric thermal injury.

Left Atrial Appendage Ligation Using the AtriClip Device: Single-Center Study of Device Safety and Efficacy.

Objective: Left atrial appendage (LAA) occlusion at the time of cardiac surgery in patients with atrial fibrillation has been shown to reduce the incidence of postoperative embolic stroke. However, the optimal method for LAA occlusion is not universally accepted. We sought to examine the safety and effectiveness of LAA occlusion with the AtriClip epicardial occlusion device. Methods: Cardiac surgical patients with atrial fibrillation who underwent LAA AtriClip placement were evaluated prospectively. Clip placement and clinical outcomes were examined after 1 year of follow-up with transesophageal echocardiography (TEE). The presence of a 10 mm or greater residual pouch, presence of flow into the LAA, or device-related thrombus (DRT) were considered failures. Results: Ninety-seven patients were analyzed. The mean CHA2DS2-VASc score was 2.4 ± 1.4. The postoperative follow-up period ranged from 366 to 1,693 days (mean 685 days or 1.87 years). Seventy-four AtriClips were placed with video-assisted thoracic surgery, whereas 23 were placed via sternotomy or thoracotomy. Successful closure was found in 96% (93 of 97) of patients at follow-up. Failure occurred in 4 patients. No clip migration or DRT was seen on 3-dimensional imaging. Of all 97 patients, 76 (78%) were on presurgical oral anticoagulation, whereas 5 (5.1%) were on postprocedure oral anticoagulation. There were no postoperative thromboembolic events at the time of the study TEE. Conclusions: The AtriClip epicardial surgical occlusion device can provide an excellent rate of successful closure of the LAA during surgical ablation procedures without DRT.

Hybrid ablation of persistent and long-standing persistent atrial fibrillation with depressed ejection fraction: A single-center observational study.

Objective: The relationship between atrial fibrillation (AF) and heart failure with depressed ejection fraction (EF) is complex. AF-related tachycardia-mediated cardiomyopathy (TMC) can lead to worsening EF and clinical heart failure. We sought to determine whether a hybrid team ablation approach (HA) can be performed safely and restore normal sinus rhythm in patients with TMC and heart failure and to delineate the effect on heart failure. Methods: We retrospectively analyzed patients with nonparoxysmal (ie, persistent and long-standing persistent) AF-related TMC with depressed left ventricular EF (LVEF ≤40%) and heart failure (New York Heart Association [NYHA] class ≥2) who underwent HA between 2013 and 2018 and had at least 1 year of follow-up. Pre-HA and post-HA echocardiograms were compared for LVEF and left atrial (LA) size. Rhythm success was defined as <30 seconds in AF/atrial flutter/atrial tachycardia without class I or III antiarrhythmic drugs. Results are expressed as mean ± SD and 95% confidence interval (CI) of the mean. Results: Forty patients met the criteria for inclusion in our analysis. The mean patient age was 67 ± 9.4 years. The majority of patients had long-standing persistent AF (26 of 40; 65%), and the remainder had persistent AF (14 of 40; 35%). All patients had NYHA class II or worse heart failure (NYHA class II, 36 of 40 [90%]; NYHA class III, 4 of 40 [10%]). The mean time in AF pre-HA was 5.6 ± 6.7 years. All patients received both HA stages. No deaths or strokes occurred within 30 days. Three new permanent pacemakers (7.5%) were placed. Rhythm success was achieved in >60% of patients during a mean 3.5 ± 1.9 years of follow-up. LVEF improved significantly by 12.0% ± 12.5% (95% CI, 7.85%-16.0%; P < .0001), and mean LA size decreased significantly by 0.40 cm ± 0.85 cm (95% CI, 0.69-0.12 cm; P < .01), with a mean of 3.0 ± 1.5 years between pre-HA and post-HA echocardiography. NYHA class improved significantly after HA (mean pre-HA NYHA class, 2.1 ± 0.3 [95% CI, 2.0-2.2]; mean post-HA NYHA class, 1.5 ± 0.6 [95% CI, 1.3-1.7]; P < .0001). Conclusions: Thoracoscopic HA of AF in selected patients with TMC heart failure is safe and can result in rhythm success with structural heart changes, including improvements in LVEF and LA size.

A heart-team hybrid approach for atrial fibrillation: a single-centre long-term clinical outcome cohort study.

OBJECTIVES: The Cox-maze IV is the gold standard for surgical ablation of atrial fibrillation (AF). A heart-team hybrid approach using selected epicardial thoracoscopic surgical ablations and completion endocardial ablations to replicate the Cox-maze IV lesion set has gained popularity and early results have been promising. We herein report our single-centre long-term clinical outcomes using the heart-team hybrid approach with 455 patients. METHODS: From 1 March 2013 to 1 July 2019, we prospectively collected data on all patients referred to our heart team for rhythm-control strategy for AF. Baseline characteristics, procedural complications and long-term freedom from AF (FFAF) both on and off anti-arrhythmic drug therapy were analysed. Ambulatory monitoring (>7 days) was obtained at 3 months and annually thereafter. RESULTS: Four hundred and fifty-five patients completed the hybrid approach. Four hundred and forty-five (97.8%) patients had non-paroxysmal AF (long-standing persistent AF n = 249, 54.7%; persistent AF n = 196, 43.1%; paroxysmal AF n = 10, 2.2%). Average duration of AF was 5.9 ± 6.1 years. Average left atrial diameter was 4.8 ± 0.8 cm. FFAF at 3, 12, 24 and 36 months was 92%, 87%, 81% and 72%, respectively. FFAF without the use of anti-arrhythmic medications was 75%, 81%, 76% and 66%. Any surgical complications occurred in 28 (6.1%) patients. CONCLUSIONS: A heart-team hybrid strategy for the treatment of AF is safe and effective. In a predominantly non-paroxysmal population with AF, at the 3-year follow-up, FFAF in patients on and off anti-arrhythmic drugs approaches that of patients who had the Cox-maze IV.