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Postoperative atrial fibrillation: from mechanisms to treatment.

ABSTRACT: Postoperative atrial fibrillation (POAF) is the most common type of secondary atrial fibrillation (AF) and despite progress in prevention and treatment, remains an important clinical problem for patients undergoing a variety of surgical procedures, and in particular cardiac surgery. POAF significantly increases the duration of postoperative hospital stay, hospital costs, and the risk of recurrent AF in the years after surgery; moreover, POAF has been associated with a variety of adverse cardiovascular events (including stroke, heart failure, and mortality), although it is still unclear if this is due to causal relation or simple association. New data have recently emerged on the pathophysiology of POAF, and new preventive and therapeutic strategies have been proposed and tested in randomized trials. This review summarizes the current evidence on the pathogenesis, incidence, prevention, and treatment of POAF and highlights future directions for clinical research.

SUBMITTER: Gaudino M

PROVIDER: S-EPMC10226752 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Postoperative atrial fibrillation: from mechanisms to treatment.

Gaudino Mario M Di Franco Antonino A Rong Lisa Q LQ Piccini Jonathan J Mack Michael M

European heart journal 20230301 12

Postoperative atrial fibrillation (POAF) is the most common type of secondary atrial fibrillation (AF) and despite progress in prevention and treatment, remains an important clinical problem for patients undergoing a variety of surgical procedures, and in particular cardiac surgery. POAF significantly increases the duration of postoperative hospital stay, hospital costs, and the risk of recurrent AF in the years after surgery; moreover, POAF has been associated with a variety of adverse cardiova ...[more]

PMID: 36721960

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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

Postoperative atrial fibrillation: from mechanisms to treatment.

Publications

Postoperative atrial fibrillation: from mechanisms to treatment.

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