Citations

Purpose: Atrial fibrillation (AF), the most common arrhythmia in older adults, is often treated with cryoballoon ablation (CBA) or laser balloon ablation (LBA) when refractory to medication. We used real-world patient data to investigate differences in arrhythmia-free survival, procedure and fluoroscopy times, and complications between these techniques. Methods: In this single-center, retrospective study of 178 patients with symptomatic paroxysmal AF referred for first-time pulmonary vein isolation (PVI), 103 underwent CBA, and 75 underwent LBA. Recurrence was defined as any atrial arrhythmia of > 30 seconds’ duration after a three-month blanking period. Complications at 30 days were recorded. Kaplan-Meier analysis was used to estimate arrhythmia-free survival at one year for both groups. Categorical variables were expressed as n (%) and continuous variables as mean ± standard deviation or median (Q1, Q3). Results: Baseline characteristics were similar between groups, with exception to left atrial volume index (CBA 32.2 ± 10.9 ml/m2; LBA 36.0 ± 11.0 ml/m2, p = 0.047). History of stroke was higher in CBA (13.6% vs 2.7%; p = 0.012), as was coronary artery disease (35.0% vs 14.7%, p = 0.002). Median fluoroscopy and procedure times (min) were significantly shorter in LBA (24.2 vs 31.6, p = 0.004; 141.0 vs 210.0, p < 0.0001, respectively). One-year arrhythmia-free survival rates were similar (CBA 79.1% vs LBA 78.7%, p = 0.934), as were total complication rates (21.4% vs 16.0%, p = 0.289), including rates of transient ischemic attack/stroke and vascular complications. Conclusions: In patients with paroxysmal AF undergoing PVI, CBA and LBA were equally efficacious at one year and demonstrated acceptably low complication rates. LBA was associated with reduced procedure time and fluoroscopy exposure.

Background Age‐related heart diseases are significant contributors to increased morbidity and mortality. Emerging evidence indicates that mitochondria within cardiomyocytes contribute to age‐related increased reactive oxygen species (ROS) generation that plays an essential role in aging‐associated cardiac diseases. Methods and Results The present study investigated differences between ROS production in cardiomyocytes isolated from adult (6 months) and aged (24 months) Fischer 344 rats, and in cardiac tissue of adult (18–65 years) and elderly (>65 years) patients with preserved cardiac function. Superoxide dismutase inhibitable ferricytochrome c reduction assay (1.32±0.63 versus 0.76±0.31 nMol/mg per minute; P =0.001) superoxide and H 2 O 2 production, measured as dichlorofluorescein diacetate fluorescence (1646±428 versus 699±329, P =0.04), were significantly higher in the aged versus adult cardiomyocytes. Similarity in age‐related alteration between rats and humans was identified in mitochondrial‐electron transport chain‐complex‐I‐associated increased oxidative‐stress by MitoSOX fluorescence (53.66±18.58 versus 22.81±12.60; P =0.03) and in 4‐HNE adduct levels (187.54±54.8 versus 47.83±16.7 ng/mg protein, P =0.0063), indicative of increased peroxidation in the elderly. These differences correlated with changes in functional enrichment of genes regulating ROS homeostasis pathways in aged human and rat hearts. Functional merged collective network and pathway enrichment analysis revealed common genes prioritized in human and rat aging‐associated networks that underlay enriched functional terms of mitochondrial complex I and common pathways in the aging human and rat heart. Conclusions Aging sensitizes mitochondrial and extramitochondrial mechanisms of ROS buildup within the heart. Network analysis of the transcriptome highlights the critical elements involved with aging‐related ROS homeostasis pathways common in rat and human hearts as targets.

Radiofrequency (RF) ablation for cardiac arrythmias is an established curative therapy. However, catheter-tip coagulum formation leading to thromboembolic stroke is a persistent problem despite heparinization. Recent studies demonstrated an up to 70% incidence of thrombus formation on the catheter tip during ablation and a 10 % incidence of thromboembolic events. Catheter tip thrombus can impede the delivery of RF energy to the tissue, resulting in reduced efficacy and longer procedure times. Here we report on a novel method to prevent coagulum formation on ablation catheters by delivering a negative charge to the catheter tip to repel negatively charged fibrinogen molecules during RF ablation. A novel circuit was built with a charge delivery unit using a 9 voltage battery to deliver a fixed offset direct current charge, placed in parallel to the RF delivery unit for negative charge placement during RF delivery. In in-vivo canine experiments (n=50) standard 6/4, 8/5 ablation catheters and catheters with abraded tips were advanced from right femoral veins into atria and ventricles under intra-cardiac echo (ICE) and biplane fluoroscopic guidance. The dogs received 1 of 2 therapies: no RF energy delivered with and without negative charge delivery, RF energy delivery with and without negative charge delivery. The presence of thrombus was identified with ICE. The catheter tips were examined also macroscopically with visual inspection and also with field emission scanning electron microscopy (FESEM). FESEM of the catheter tips showed surface coverage of fibrin clot of the catheter tip to be 90 % for non-charged catheters compared to 0 % (p< 0.01) in negatively-charged catheters. There was no significant difference in surface coverage of fibrin clot between negatively-charged catheters with the abraded tips (98.8%) and non-charged catheters with smooth tips (90.7 %, p=ns). Clot volume formed on the catheter tip decreased with increased amount of charge. Application of a negative charge did not affect the quality of the intracardiac electrograms or induce malignant ventricular arrhythmias. Negative charge delivery during RF ablation is feasible and safe and can eliminate coagulum formation, potentially reducing thromboembolic complications.

Background : Lipid lowering therapy reduces mortality in patients with both ischemic and nonischemic cardiomyopathies and recently has been shown to decrease ICD shocks. Radiofrequency ablation (RFA) of recurrent VT in patients with an ICD also reduces shocks following intervention. It is unclear if statin therapy after VT RFA will further impact ICD shock rates. Methods : All patients from 1993–2005 who underwent a RFA procedure for recurrent VT at the Mayo Clinic with an ICD were included. Patient records were extracted for medical and procedural details and all ICD interrogations were reviewed for VT recurrence and therapies. Results: 63 patients (age 62±15 years) were followed over 3.9±3.6 years. Comorbid diseases included: coronary artery disease 37(58%, 34 prior myocardial infarction), ARVD/C 6(10%), nonischemic dilated cardiomyopathy 7(11%), moderate-severe valve disease 14(22%), hypertension 34(54%), and hyperlipidemia 35(56%). Ejection fraction was <0.35 in 34(56%). VT was induced in all patients (LV 55 (LVOT 1), RV 8 (RVOT 3) with multiple inducible VTs in 21(33%). VT was noninducible after RFA in 39(62%) patients. Dismissal medications included: statins 19(30%), beta blockers 40(66%), ACE/ARB 37(61%), diuretics 34(55%), and digoxin 23(37%). 5-year overall survival was 63%(95% CI 55–71). Age, diabetes, and renal insufficiency were associated with increased post ablation mortality, with no medication improving survival. 5-year survival free of ICD shocks was 31%(95% CI 24–38). Only statin therapy at discharge was associated with a decreased risk of ICD shocks [5(26%) versus 26(59%), p=0.020]. 7 additional patients received statins during follow-up, but not at discharge, of these 5(71%) had shocks. Conclusion : Statin use at discharge in patients with an ICD undergoing RFA for refractory VT significantly reduced recurrent ventricular arrhythmias and ICD shocks. Although the mechanism underlying the effects of statins on arrhythmic recurrence early after RFA requires further study, these data support aggressive therapy of the underlying substrate responsible for the VT.

Estrogen receptor beta (βER) is present in platelets but little is known about how βER contributes to platelet physiology. Platelet mitochondrial function and circulating platelet‐derived microparticles were analyzed in aged (24 months old) female wild type (WT) and estrogen receptor beta knockout (βERKO) mice. In intact, unstimulated platelets, ERβ did not co‐localized with mitochondria. Platelet lactate production, mitochondrial membrane potential and superoxide generation were similar in both groups, but activities of cytochrome bc 1 and cytochrome c oxidase were significantly less (P<0.05) in platelets of βERKO mice. Total numbers of platelet‐derived microparticles and those positive for procoagulant phosphatidylserine (PS) were two to three times higher (P<0.05) in βERKO than WT mice. Greater than 40% of procoagulant microparticles were derived from cells other than platelets in both groups of mice. Thrombin generating capacity of microvesicles was also greater in βERKO mice. Thus, loss of βER leads to significant changes in activities of enzymes of the mitochondrial electron transport system, and to increases in circulating procoagulant microparticles which may contribute to an increased thrombotic risk with aging in persons with βER gene polymorphisms. This study is supported by HL78638, AHA30503Z and Mayo Foundation.

Introduction: Although alterations in mitochondrial function have been observed in senescent hearts, the molecular basis for aging-associated decline in energy metabolism in the human heart is not fully understood. Objective: To determine aging-related changes in functional activity and protein expression level of mitochondrial oxidative phosphorylation (OXPHOS) complexes and expression of genes regulating mitochondrial energetics in the human heart. Methods: Right atrial appendages from well-matched adult (29-57 y.o., n=19) and aged (65-85 y.o., n=22) patients undergoing elective CABG surgery were used. Functional activity of OXPHOS complexes was measured spectrophotometrically. Protein expression level of corresponding OXPHOS protein subunits was determined by Western blot. Gene expression profiling was performed using Affymetrix Human Genome U133 Plus 2.0 microarrays. Results: Mitochondria from senescent hearts demonstrated a significant decrease in complex I and V functional activity without significant changes in the rest of the complexes (Fig. A). At the protein expression level, there was reduction in complex I, III, and IV (Fig. B). This was associated with downregulation of the majority (86%, 90 of 105) of genes coding mitochondrial proteins (Fig. C). Forty-six percent (41 of 90) of the downregulated genes were confined to pathways regulating mitochondrial energetics. Conclusion: With aging, the functional activity of OXPHOS is reduced due to supression of protein expression and downregulation of genes regulating mitochondrial energetics. This provides a substrate for reduced energetic efficiency associated with senescence in the human atria.