miR-199a-5p Is Upregulated during Fibrogenic Response to Tissue Injury and Mediates TGFbeta-Induced Lung Fibroblast Activation by Targeting Caveolin-1

As miRNAs are associated with normal cellular processes, deregulation of miRNAs is thought to play a causative role in many complex diseases. Nevertheless, the precise contribution of miRNAs in fibrotic lung diseases, especially the idiopathic form (IPF), remains poorly understood. Given the poor response rate of IPF patients to current therapy, new insights into the pathogenic mechanisms controlling lung fibroblasts activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies for this devastating disease. To identify miRNAs with potential roles in lung fibrogenesis, we performed a genome-wide assessment of miRNA expression in lungs from two different mouse strains known for their distinct susceptibility to develop lung fibrosis after bleomycin exposure. This led to the identification of miR-199a-5p as the best miRNA candidate associated with bleomycin response. Importantly, miR-199a-5p pulmonary expression was also significantly increased in IPF patients (94 IPF versus 83 controls). In particular, levels of miR-199a-5p were selectively increased in myofibroblasts from injured mouse lungs and fibroblastic foci, a histologic feature associated with IPF. Therefore, miR-199a-5p profibrotic effects were further investigated in cultured lung fibroblasts: miR-199a-5p expression was induced upon TGFβ exposure, and ectopic expression of miR-199a-5p was sufficient to promote the pathogenic activation of pulmonary fibroblasts including proliferation, migration, invasion, and differentiation into myofibroblasts. In addition, we demonstrated that miR-199a-5p is a key effector of TGFβ signaling in lung fibroblasts by regulating CAV1, a critical mediator of pulmonary fibrosis. Remarkably, aberrant expression of miR-199a-5p was also found in unilateral ureteral obstruction mouse model of kidney fibrosis, as well as in both bile duct ligation and CCl4-induced mouse models of liver fibrosis, suggesting that dysregulation of miR-199a-5p represents a general mechanism contributing to the fibrotic process. MiR-199a-5p thus behaves as a major regulator of tissue fibrosis with therapeutic potency to treat fibroproliferative diseases. © 2013 Lino Cardenas et al

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Resetting criteria during ventricular overdrive pacing successfully differentiate orthodromic reentrant tachycardia from atrioventricular nodal reentrant tachycardia despite interobserver disagreement concerning QRS fusion

Background The beginning of ventricular overdrive pacing (VOP) during supraventricular tachycardia (SVT) accurately distinguishes orthodromic reentrant tachycardia (ORT) from atrioventricular nodal reentrant tachycardia (AVNRT) even when pacing terminates tachycardia. Tachycardia resetting most often occurs during this transition zone (TZ) of QRS fusion in ORT and after this TZ in AVNRT. The end of the TZ is marked by the first beat with a stable QRS morphology but is a subjective assessment. Disagreement concerning this beat may change tachycardia diagnosis. Objective The purpose of this study was to assess interobserver agreement for identifying the TZ and whether disagreement affected diagnosis. Methods Seventy-nine consecutive patients with inducible ORT and AVNRT were included. Resetting of tachycardia was evaluated by (1) atrial timing perturbation and (2) fixed stimulationatrial activation timing (SA). Two blinded observers identified the end of the TZ and used the two resetting criteria to establish a diagnosis. Diagnostic results were compared with standard criteria for SVT diagnosis. The diagnosis was considered correct if both electrophysiologists\u27 TZ assessment resulted in a correct diagnosis. Results Agreement on the TZ occurred in 80% (148/186) of VOP trains. In ORT patients, tachycardia resetting occurred during the TZ and correctly diagnosed ORT based on atrial timing perturbation and fixed SA in 91% and 98% of VOP trains, respectively. In AVNRT patients, tachycardia resetting occurred after the TZ and correctly diagnosed AVNRT based on atrial timing perturbation and fixed SA in 93% and 94% of VOP trains, respectively. Conclusion Resetting criteria used during the VOP TZ accurately differentiate between ORT and AVNRT despite interobserver disagreement concerning identification of the TZ. © 2011 Heart Rhythm Society

Quality of life with atrial fibrillation: Do the spouses suffer as much as the patients?

Background: Atrial fibrillation (AF) can have a significant effect on quality of life (QoL). Other chronic diseases are known to not only affect the patient but to also impact the QoL of persons living with them. Scant data exist on the QoL effect of AF in spouses/significant others (SOs). Methods: An anonymous survey regarding the perceived effect of AF on QoL was designed and distributed to both patients and spouses/SOs during an educational symposium about living with AF. Both were asked to fill out the survey independently according to how their life was affected by either their AF or their partner\u27s AF. Questions included demographics, perceived impairment of overall QoL on a 5-point scale, as well as effect on subcategories of QoL, namely daily activity, work life, sex life, physical activity, psychological well-being, and social activity. Results: Five hundred and sixty-eight subjects completed the survey of which 411 were AF patients and 129 were spouses/SOs. The perceived effect of AF on overall QoL (N = 527) was similar in patients and spouses (AF patients: mild 42.0%, moderate 26.0%, severe 32.0% vs. spouses: 44.1%, 25.2%, 31.7%; P = 0.917). This result did not change when adjusted for age and gender. There was also no significant difference between patients and spouses in the subcategories of QoL with the exception of the perceived effect on work life, which was greater in patients than spouses (P = 0.041). Conclusions: AF has a similar perceived impact on the QoL of spouses and patients. QoL improvement strategies for patients with AF should take spouses into account. © 2011 Wiley Periodicals, Inc

Family history of atrial fibrillation as a predictor of atrial substrate and arrhythmia recurrence in patients undergoing atrial fibrillation catheter ablation

© Published on behalf of the European Society of Cardiology. All rights reserved. Aims A commonly held notion is that patients with a family history of atrial fibrillation (AF) have worse atrial substrate and higher rates of arrhythmia recurrence following ablation. We sought to examine differences in atrial substrate and catheter ablation outcomes in patients with a 1st degree family member with paroxysmal or persistent AF (PeAF) compared to those without. Methods and results A total of 256 consecutive patients undergoing their 1st ablation for AF (123 paroxysmal, 133 persistent) with \u3e1 year follow up were included. The presence of one 1st-degree family relative was defined as a \u27positive family history\u27. Clinical characteristics, electroanatomic map findings, ablation characteristics and outcomes were compared in patients with and without a positive family history of AF. Patients with paroxysmal fibrillation with a positive family history (n = 57; 46%) had similar clinical characteristics and arrhythmia recurrence after catheter ablation as those without. Of those that recurred, patients with a positive family history were more likely to have progressed to PeAF (P = 0.05). Patients with PeAF with a positive family history (n = 75; 56%) had similar clinical characteristics, electroanatomic mapping findings and ablation characteristics, but worse long term arrhythmia free survival (P = 0.04). Conclusion The presence of a 1st-degree family member with AF does not impact the clinical outcomes of catheter ablation for paroxysmal AF. However, a positive family history is associated with worse arrhythmia free survival in patients with PeAF. This finding is not explained by differences in clinical characteristics, atrial substrate assessed by voltage maps or ablation characteristics

Percutaneous access of the epicardial space for mapping ventricular and supraventricular arrhythmias in patients with and without prior cardiac surgery

There is a paucity of data on the success rates of achieving percutaneous epicardial access in different groups of patients

Transcoronary ethanol ablation for recurrent ventricular tachycardia after failed catheter ablation: An update

Background-Despite substantial progress, radiofrequency catheter ablation (RFCA) fails in some patients. After encouraging results with transcoronary ethanol ablation (TCEA), we began offering TCEA routinely when endocardial and epicardial RFCA failed or a deep intramural substrate was likely. Methods and Results-Among 274 consecutive patients who underwent 408 ventricular tachycardia (VT) ablation procedures, 27 patients (21 men; age, 63±13 years; left ventricular ejection fraction, 30±11%; ischemic cardiomyopathy, 14) had 29 TCEA procedures attempted. In 5 patients, TCEA was abandoned because of unfavorable anatomy. In 22 patients, a mean of 1.3±0.6 arteries (range, 1-3 arteries) were targeted for TCEA. After ablation, the targeted VT was no longer inducible in 18 of 22 (82%) patients. Complete heart block occurred in 5 patients, and 3 patients with advanced heart failure died within 30 days of the procedure. After the last TCEA procedure, a VT recurred in 64% of patients, and overall, 32% of patients died. Of 11 patients with prior VT storm, 9 were free of VT storm. At repeat study in 8 patients who had a recurrence, 7 had a new QRS morphology of VT originating from the same general substrate region as the prior VT. Conclusions-In patients with difficult-to-control VT in whom RFCA fails, TCEA prevents all VT recurrences in 36% and improves arrhythmia control in an additional 27%. Inadequate target vessels, collaterals, and recurrence of modified VTs limit efficacy, but TCEA continues to play an important role for difficult VTs in these high-risk patients. © 2011 American Heart Association, Inc

Role of alternative interventional procedures when endo- and epicardial catheter ablation attempts for ventricular arrhythmias fail.

BACKGROUND Ventricular tachycardia (VT) refractory to antiarrhythmic drugs and standard percutaneous catheter ablation techniques portends a poor prognosis. We characterized the reasons for ablation failure and describe alternative interventional procedures in this high-risk group. METHODS AND RESULTS Sixty-seven patients with VT refractory to 4±2 antiarrhythmic drugs and 2±1 previous endocardial/epicardial catheter ablation attempts underwent transcoronary ethanol ablation, surgical epicardial window (Epi-window), or surgical cryoablation (OR-Cryo; age, 62±11 years; VT storm in 52%). Failure of endo/epicardial ablation attempts was because of VT of intramural origin (35 patients), nonendocardial origin with prohibitive epicardial access because of pericardial adhesions (16), and anatomic barriers to ablation (8). In 8 patients, VT was of nonendocardial origin with a coexisting condition also requiring cardiac surgery. Transcoronary ethanol ablation alone was attempted in 37 patients, OR-Cryo alone in 21 patients, and a combination of transcoronary ethanol ablation and OR-Cryo (5 patients), or transcoronary ethanol ablation and Epi-window (4 patients), in the remainder. Overall, alternative interventional procedures abolished ≥1 inducible VT and terminated storm in 69% and 74% of patients, respectively, although 25% of patients had at least 1 complication. By 6 months post procedures, there was a significant reduction in defibrillator shocks (from a median of 8 per month to 1; P<0.001) and antiarrhythmic drug requirement although 55% of patients had at least 1 VT recurrence, and mortality was 17%. CONCLUSIONS A collaborative strategy of alternative interventional procedures offers the possibility of achieving arrhythmia control in high-risk patients with VT that is otherwise uncontrollable with antiarrhythmic drugs and standard percutaneous catheter ablation techniques