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Atrial Substrate Modification in Atrial Fibrillation: Targeting GP or CFAE? Evidence from Meta-Analysis of Clinical Trials.

ABSTRACT: Several clinically relevant outcomes post atrial substrate modification in patients with atrial fibrillation (AF) have not been systematically analyzed among published studies on adjunctive cardiac ganglionated plexi (GP) or complex fractionated atrial electograms (CFAE) ablation vs. pulmonary vein isolation (PVI) alone. Out of 176 reports identified, the present meta-analysis included 14 randomized and non-randomized controlled trials (1613 patients) meeting inclusion criteria. Addition of GP ablation to PVI significantly increased freedom from atrial tachyarrhythmia in short- (OR: 1.72; P = 0.003) and long-term (OR: 2.0, P = 0.0006) follow-up, while adjunctive CFAE ablation did not after one or repeat procedure (P<0.05). The percentage of atrial tachycardia or atrial flutter (AT/AFL) after one procedure was higher for CFAE than GP ablation. In sub-analysis of non-paroxysmal AF, relative to PVI alone, adjunctive GP but not CFAE ablation significantly increased sinus rhythm maintenance (OR: 1.88, P = 0.01; and OR:1.24, P = 0.18, respectively). Meta regression analysis of the 14 studies indicated that sample size was significant source of heterogeneity either in outcomes after one or repeat procedure. In conclusion, in patients with AF, adjunctive GP but not CFAE ablation appeared to significantly add to the beneficial effects on sinus rhythm maintenance of PVI ablation alone; and CFAE ablation was associated with higher incidence of subsequent AT/AFL.

SUBMITTER: Qin M

PROVIDER: S-EPMC5072654 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Atrial Substrate Modification in Atrial Fibrillation: Targeting GP or CFAE? Evidence from Meta-Analysis of Clinical Trials.

Qin Mu M Liu Xu X Wu Shao-Hui SH Zhang Xiao-Dong XD

PloS one 20161020 10

Several clinically relevant outcomes post atrial substrate modification in patients with atrial fibrillation (AF) have not been systematically analyzed among published studies on adjunctive cardiac ganglionated plexi (GP) or complex fractionated atrial electograms (CFAE) ablation vs. pulmonary vein isolation (PVI) alone. Out of 176 reports identified, the present meta-analysis included 14 randomized and non-randomized controlled trials (1613 patients) meeting inclusion criteria. Addition of GP a ...[more]

PMID: 27764185

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Project description:RationalePostoperative atrial fibrillation (POAF) is a common and troublesome complication of cardiac surgery. POAF is generally believed to occur when postoperative triggers act on a preexisting vulnerable substrate, but the underlying cellular and molecular mechanisms are largely unknown.ObjectiveTo identify cellular POAF mechanisms in right atrial samples from patients without a history of atrial fibrillation undergoing open-heart surgery.Methods and resultsMulticellular action potentials, membrane ion-currents (perforated patch-clamp), or simultaneous membrane-current (ruptured patch-clamp) and [Ca2+]i-recordings in atrial cardiomyocytes, along with protein-expression levels in tissue homogenates or cardiomyocytes, were assessed in 265 atrial samples from patients without or with POAF. No indices of electrical, profibrotic, or connexin remodeling were noted in POAF, but Ca2+-transient amplitude was smaller, although spontaneous sarcoplasmic reticulum (SR) Ca2+-release events and L-type Ca2+-current alternans occurred more frequently. CaMKII (Ca2+/calmodulin-dependent protein kinase-II) protein-expression, CaMKII-dependent phosphorylation of the cardiac RyR2 (ryanodine-receptor channel type-2), and RyR2 single-channel open-probability were significantly increased in POAF. SR Ca2+-content was unchanged in POAF despite greater SR Ca2+-leak, with a trend towards increased SR Ca2+-ATPase activity. Patients with POAF also showed stronger expression of activated components of the NLRP3 (NACHT, LRR, and PYD domains-containing protein-3)-inflammasome system in atrial whole-tissue homogenates and cardiomyocytes. Acute application of interleukin-1β caused NLRP3-signaling activation and CaMKII-dependent RyR2/phospholamban hyperphosphorylation in an immortalized mouse atrial cardiomyocyte cell-line (HL-1-cardiomyocytes) and enhanced spontaneous SR Ca2+-release events in both POAF cardiomyocytes and HL-1-cardiomyocytes. Computational modeling showed that RyR2 dysfunction and increased SR Ca2+-uptake are sufficient to reproduce the Ca2+-handling phenotype and indicated an increased risk of proarrhythmic delayed afterdepolarizations in POAF subjects in response to interleukin-1β.ConclusionsPreexisting Ca2+-handling abnormalities and activation of NLRP3-inflammasome/CaMKII signaling are evident in atrial cardiomyocytes from patients who subsequently develop POAF. These molecular substrates sensitize cardiomyocytes to spontaneous Ca2+-releases and arrhythmogenic afterdepolarizations, particularly upon exposure to inflammatory mediators. Our data reveal a potential cellular and molecular substrate for this important clinical problem.

Dataset Information

Atrial Substrate Modification in Atrial Fibrillation: Targeting GP or CFAE? Evidence from Meta-Analysis of Clinical Trials.

Publications

Atrial Substrate Modification in Atrial Fibrillation: Targeting GP or CFAE? Evidence from Meta-Analysis of Clinical Trials.

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