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.
It is unknown whether radiofrequency ablation (RFA) or antiarrhythmic therapy is superior when treating patients with symptomatic premature ventricular contractions (PVCs).
To determine the relative ...efficacy of RFA and antiarrhythmic drugs (AADs) on PVC burden reduction and increasing left ventricular systolic function.
Patients with frequent PVCs (>1000/24 h) were treated either by RFA or with AADs from January 2005 through December 2010. Data from 24-hour Holter monitoring and echocardiography before and 6-12 months after treatment were compared between the 2 groups.
Of 510 patients identified, 215 (40%) underwent RFA and 295 (60%) received AADs. The reduction in PVC frequency was greater by RFA than with AADs (-21,799/24 h vs -8,376/24 h; P < .001). The left ventricular ejection fraction (LVEF) was increased significantly after RFA (53%-56%; P < .001) but not after AAD (52%- 52%; P = .6) therapy. Of 121 (24%) patients with reduced LVEF, 39 (32%) had LVEF normalization to 50% or greater. LVEF was restored in 25 of 53 (47%) patients in the RFA group compared with 14 of 68 (21%) patients in the AAD group (P = .003). PVC coupling interval less than 450 ms, less impaired left ventricular function, and RFA were independent predictors of LVEF normalization performed by using multivariate analysis.
RFA appears to be more effective than AADs in PVC reduction and LVEF normalization.
OBJECTIVE To evaluate the prevalence and pathogenetic mechanisms of postural orthostatic tachycardia syndrome (POTS). PATIENTS AND METHODS We reviewed the medical records of patients with POTS seen ...at the Mayo Clinic in Rochester, Minn, from January 1, 1993, through December 31, 2003. All patients were required to have had a full autonomic reflex screen. The results of the following additional tests were evaluated: thermoregulatory sweat test, plasma catecholamine measurement, serum ganglionic (α3) acetylcholine receptor antibody detection, and 24-hour urinary sodium measurement. RESULTS We identified 152 patients (86.8% female; mean ± SD age, 30.2±10.3 years) with a mean duration of symptoms of 4.1 years. The mean orthostatic heart rate increment was 44 beats/min. Half the patients had sudomotor abnormalities (apparent on both the quantitative sudomotor axon reflex test and thermoregulatory sweat test), and 34.9% had significant adrenergic impairment, indicating that at least half of the patients had a neuropathic pattern of POTS. In 13.8% of patients, onset was subacute, and ganglionic acetylcholine receptor antibody was detected in 14.6%, suggesting an autoimmune origin in at least 1 in 7 patients. Hyperadrenergic status was documented in 29.0% of patients (standing plasma norepinephrine level ≥600 pg/mL), and at least 28.9% were presumably hypovolemic (24-hour urinary sodium level <100 mEq/24h). The lack of correlation between urinary sodium and standing norepinephrine levels suggests that mechanisms other than hypovolemia accounted for the hyperadrenergic state. CONCLUSION Our findings suggest a neuropathic basis for at least half the cases of POTS and that a substantial percentage of cases may be autoimmune. Hyperadrenergic and hypovolemic correlates are likely compensatory or exacerbating.
Objectives The authors sought to characterize the left atrial (LA) and pulmonary vein (PV) electrophysiological and hemodynamic features in obese patients with atrial fibrillation (AF). Background ...Obesity is associated with increased risk for AF. Methods A total of 63 consecutive patients with AF who had normal left ventricular (LV) ejection fraction and who underwent catheter ablation were studied. Atrial and PV electrophysiological studies were performed at the time of ablation with hemodynamic assessment by cardiac catheterization, and LA/LV structure and function by echocardiography. Patients were compared on the basis of body mass index (BMI): <25 kg/m2 (n = 19) and BMI ≥30 kg/m2 (n = 44). Results At a 600-ms pacing cycle length, obese patients had shorter effective refractory period (ERP) in the left atrium (251 ± 25 ms vs. 233 ± 32 ms, p = 0.04), and in the proximal (207 ± 33 ms vs. 248 ± 34 ms, p < 0.001) and distal (193 ± 33 ms vs. 248 ± 44 ms, p < 0.001) PV than normal BMI patients. Obese patients had higher mean LA pressure (15 ± 5 mm Hg vs. 10 ± 5 mm Hg, p < 0.001) and LA volume index (28 ± 12 ml/m2 vs. 21 ± 14 ml/m2 , p = 0.006), and lower LA strain (5.5 ± 3.1% vs. 8.8 ± 2.8%; p < 0.001) than normal BMI patients. Conclusions Increased LA pressure and volume, and shortened ERP in the left atrium and PV are potential factors facilitating and perpetuating AF in obese patients with AF.
Sleep disturbance caused by obstructive sleep apnea is recognized as a contributing factor to adverse cardiovascular outcomes. However, the effect of restless legs syndrome, another common cause of ...fragmented sleep, on cardiac structure, function, and long-term outcomes is not known. The aim of this study was to assess the effect of frequent leg movement during sleep on cardiac structure and outcomes in patients with restless legs syndrome.
In our retrospective study, patients with restless legs syndrome referred for polysomnography were divided into those with frequent (periodic movement index > 35/hour) and infrequent (≤ 35/hour) leg movement during sleep. Long-term outcomes were determined using Kaplan-Meier and logistic regression models.
Of 584 patients, 47% had a periodic movement index > 35/hour. Despite similarly preserved left ventricular ejection fraction, the group with periodic movement index > 35/hour had significantly higher left ventricular mass and mass index, reflective of left ventricular hypertrophy (LVH). There were no significant baseline differences in the proportion of patients with hypertension, diabetes, hyperlipidemia, prior myocardial infarction, stroke or heart failure, or the use of antihypertensive medications between the groups. Patients with frequent periodic movement index were older, predominantly male, and had more prevalent coronary artery disease and atrial fibrillation. However, on multivariate analysis, periodic movement index > 35/hour remained the strongest predictor of LVH (odds ratio, 2.45; 95% confidence interval, 1.67-3.59; P < .001). Advanced age, female sex, and apnea-hypopnea index were other predictors of LVH. Patients with periodic movement index > 35/hour had significantly higher rates of heart failure and mortality over median 33-month follow-up.
Frequent periodic leg movement during sleep is an independent predictor of severe LVH and is associated with increased cardiovascular morbidity and mortality.
PDF
