MicroRNAs are important regulators of gene expression, including those involving electrical remodeling in atrial fibrillation (AF). Recently, KCNN3, the gene that encodes the small-conductance ...calcium-activated potassium channel 3 (SK3), was found to be strongly associated with AF.
To evaluate the changes in atrial myocardial microRNAs in patients with permanent AF and to determine the role of microRNA on the regulation of cardiac SK3 expression.
Atrial tissue obtained during cardiac surgery from patients (4 sinus rhythm and 4 permanent AF) was analyzed by using microRNA arrays. Potential targets of microRNAs were predicted by using software programs. The effects of specific microRNAs on target gene expression were evaluated in HL-1 cells from a continuously proliferating mouse hyperplastic atrial cardiomyocyte cell line. Interactions between microRNAs and targets were further evaluated by using luciferase reporter assay and by using Argonaute pull-down assay.
Twenty-one microRNAs showed significant (>2-fold) changes in AF. MicroRNA 499 (miR-499) was upregulated by 2.33-fold (P < .01) in AF atria, whereas SK3 protein expression was downregulated by 46% (P < .05). Transfection of miR-499 mimic in HL-1 cells resulted in the downregulation of SK3 protein expression, while that of miR-499 inhibitor upregulated SK3 expression. Binding of miR-499 to the 3' untranslated region of KCNN3 was confirmed by luciferase reporter assay and by the increased presence of SK3 mRNA in Argonaute pulled-down microRNA-induced silencing complexes after transfection with miR-499.
Atrial miR-499 is significantly upregulated in AF, leading to SK3 downregulation and possibly contributing to the electrical remodeling in AF.
Epicardial adipose tissue (EAT) has been recognized as a sensitive marker of cardiometabolic risk. Recent evidence suggests efficacy of long-term statin therapy in reducing EAT in patients with ...coronary artery disease. Whether short-term statin therapy is associated with changes in the volume of EAT is currently unknown. A cohort of patients with atrial fibrillation who underwent pulmonary vein isolation were randomized to receive either 80 mg/day of atorvastatin (n = 38, 32 men, age 56 ± 11 years) or placebo (n = 41, 33 men, age 56 ± 10 years) for a 3-month period. EAT volume was assessed by cardiac computed tomography at baseline and at follow-up. Patients randomized to statin treatment exhibited a modest but significant decrease in median EAT volume (baseline vs follow-up: 92.3 cm3 62.0 to 133.3 vs 86.9 cm3 64.1 to 124.8, p <0.05), whereas median EAT remained unchanged in the placebo group (81.9 cm3 55.5 to 110.9 vs 81.3 cm3 57.1 to 110.5, p = NS). Changes in median systemic inflammatory markers and lipid profile were also seen with statin treatment: C-reactive protein (2.4 mg/L 0.7 to 3.7 vs 1.1 mg/L 0.5 to 2.7, p <0.05), total cholesterol (186 mg/dL 162.5 to 201 vs 123 mg/dL 99 to 162.5, p <0.001), and low-density lipoprotein cholesterol (116 mg/dL 96.5 to 132.5 vs 56 40.5 to 81 mg/dL, p <0.001) diminished, whereas median body mass index did not change (27.8 kg/m2 25 to 30 versus 27.6 kg/m2 25.7 to 30.5, p = NS). No variations occurred in the placebo group. In conclusion, short-term intensive statin therapy significantly reduced the volume of EAT in patients with atrial fibrillation.
It is known that statins are effective in preventing atrial fibrillation (AF) in patients undergoing cardiac surgery.
The purpose of this study was to evaluate the efficacy of statins in preventing ...AF recurrence following left atrial ablation.
One hundred twenty-five patients who had no statin indication undergoing catheter ablation due to drug-refractory paroxysmal (n = 90) or persistent (n = 35) AF were randomized in a prospective, double-blind, placebo-controlled trial to receive 80 mg atorvastatin (n = 62) or placebo (n = 63) for 3 months. The primary endpoint was freedom from symptomatic AF at 3 months. Secondary endpoints included freedom from any atrial arrhythmia recurrence irrespective of symptoms, quality of life (QoL), and reduction in C-reactive protein (CRP).
At 3 months, 95% of patients in the atorvastatin group were free of symptomatic AF compared with 93.5% in the placebo group (P = .75). Similarly, 85% of patients treated in the atorvastatin group remained free of any recurrent atrial arrhythmia vs 88% of patients in the placebo group (P = .37). Mean CRP levels decreased in the atorvastatin group (mean change -0.75 ± 3, P = .02) and increased in the placebo group (mean change 2.1 ± 19.9, P = .48). Mean QoL score improved significantly in both groups (mean change 13.14 ± 18.2 in the atorvastatin group and 11.10 ± 17.7 in the placebo group, P = .53).
In patients with no standard indication for statin therapy, treatment with atorvastatin 80 mg/day following AF ablation does not decrease the risk of AF recurrence in the first 3 months and should not be routinely administered to prevent periprocedural arrhythmias.
Dual-chamber implantable cardioverter-defibrillators (ICDs) may improve specificity and reduce the risk of inappropriate shocks, and enhance atrial arrhythmia (AT/AF) detection to permit stroke ...prevention compared with single-chamber ICDs, but at additional expense and risk.
Patients (n = 100) receiving primary prevention ICDs at two USA and two Israeli centres were randomized to dual-chamber or single-chamber devices between December 2008 and December 2010 and were followed for 1 year. Programming in both groups included: delayed detection to avoid therapy for non-sustained episodes; high detection cut-off rates to avoid treating slower, better tolerated arrhythmias; minimized right ventricular pacing; and routine use of supraventricular-ventricular tahcycardia discriminators and antitachycardia pacing. The primary outcome was the proportion of patients with inappropriate shocks. One patient in each group (2%) received inappropriate shocks (P = 1.00). Death occurred in two patients in the single-chamber arm, and in none of the patients in the dual-chamber arm (P = 0.15). New AT/AF was detected in 12 patients (24%) in the dual-chamber group, vs. no patients in the single-chamber group (P < 0.001). Among US participants, the mean cost of dual- vs. single-chamber ICD implantation was $16 579 vs. $14 249, respectively (P < 0.001); there was no difference in the quality of life (EQ-5D index difference 0.013, P = 0.769; EQ VAS difference 3.3, P = 0.49).
When optimal programming is utilized, inappropriate shocks are rare in primary prevention patients with both single- and dual-chamber ICDs. The routine use of dual-chamber ICDs increases the expense without reducing inappropriate shocks or improving the quality of life at 1 year.
clinicaltrials.gov Identifier: NCT00787800.
Risk Factors for ICD Lead Fracture. Introduction: The Medtronic Sprint Fidelis® implantable cardioverter defibrillator (ICD) lead was “recalled” in October 2007 after 268,000 implants worldwide due ...to increased failure risk. Manufacturer suggested monitoring has not been shown effective at preventing adverse events. Only limited data exist regarding clinical predictors of Fidelis® lead fracture. We sought to identify risk factors for Fidelis® fracture to guide clinical monitoring and compare its performance with a control lead.
Methods:
Fractured lead cases were retrospectively reviewed for demographic data, implant technique, radiographic appearance and clinical presentation was analyzed. Lead survival was compared using Kaplan‐Meir curves.
Results:
Study patients (n = 1314) experienced 18 Fidelis® and 6 Quattro™ lead fractures. Patients with failed Fidelis® leads were younger than those with surviving leads (49.5 vs 64.6 years, P = 0.0066). Fidelis® lead fractures often occurred around the time of physical activity. No other measured demographic or technique related factors were associated with lead fracture. Fidelis® leads had significantly decreased survival compared with Quattro™ leads (89.3 vs 98.9% at 30 months). Patients less than 50 years old had significantly decreased lead survival compared with those older than 50 in both Fidelis® (79.6% vs 96.5% at 24 months) and Quattro™ (93.4 vs 99.8%, P < 0.001 at 24 months) leads.
Conclusions:
Patients under age 50, with either Fidelis® or Quattro™ ICD leads, are at increased risk of lead fracture compared with patients over 50, particularly around the time of intense physical activity. Aggressive monitoring and advisory programming appears warranted in patients with Fidelis® leads as well as especially in younger patients. (J Cardiovasc Electrophysiol, Vol. 21, pp. 671‐677, June 2010)
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