What is the clinical evidence from this study?

Study design: RCT. Population: Atrial Fibrillation (n=28). Intervention: Atrial tachypacing (A-TP) vs. Sham operation. Primary outcome: Left ventricular ejection fraction (LVEF) (p=0.001).

April 9, 2020Open Access

Characterization of Atrial and Ventricular Structural Remodeling in a Porcine Model of Atrial Fibrillation Induced by Atrial Tachypacing

Key Result

Atrial tachypacing-induced atrial fibrillation significantly reduced left ventricular ejection fraction to 48% compared to 68% in sham controls, and increased atrial and ventricular fibrosis.

Study Design

Type

RCT (n=28)

Blinding

Blinded analysis

Randomization

Randomized

Multicenter

Structured PICO

Does right atrial tachypacing induce structural and functional remodeling in a porcine model?

Population

28 Landrace pigs (large animal model)

Intervention

Right atrial tachypacing (A-TP) for 43±4 days until sustained atrial fibrillation

Comparator

Control group (14 pigs)

Outcome

Functional remodeling (investigated by echocardiography) and structural remodeling (quantified by histological preparations and immunohistochemical stainings)surrogate

Right atrial tachypacing in a porcine model effectively induces atrial fibrillation with concomitant left ventricular dysfunction and bi-atrial/ventricular fibrosis, providing a robust model for AF-induced remodeling.

Main Result

Absolute Event Rate: 48% vs 68%

p-value: p=0.001

Limitations

High mortality/dropout in the A-TP group (5 pigs died or were euthanized early due to heart failure)
Vimentin is not unique to fibroblasts, potentially overestimating fibroblast counts
The trained system for image analysis tends to slightly overestimate fibrosis
Lack of α-SMA staining to confirm myofibroblasts
Anesthetic regimen may have influenced hemodynamic parameters
Small sample size
Only female pigs (gilts) were used

Abstract

Background: Atrial fibrillation (AF) is characterized by electrical and structural remodeling. Irregular and/or fast atrio-ventricular (AV) conduction during AF can result in AV dyssynchrony, tachymyopathy, pressure and volume overload with subsequent dilatation, valve regurgitation, and ventricular dysfunction with progression to heart failure. Objective: To gain further insight into the myocardial pathophysiological changes induced by right atrial tachypacing (A-TP) in a large animal model. Methods: A total of 28 Landrace pigs were randomized as 14 into AF-induced A-TP group and 14 pigs to control group. AF pigs were tachypaced for 43±4 days until in sustained AF. Functional remodeling was investigated by echocardiography (after cardioversion to sinus rhythm). Structural remodeling was quantified by histological preparations with picrosirius red and immunohistochemical stainings. Results: A-TP resulted in decreased left ventricular ejection fraction (LVEF) accompanied by increased end-diastolic and end-systolic left atrium (LA) volume and area. In addition, A-TP was associated with mitral valve (MV) regurgitation, diastolic dysfunction and increased atrial and ventricular fibrotic extracellular matrix (ECM). Conclusions: A-TP induced AF with concomitant LV systolic and diastolic dysfunction, increased LA volume and area, and atrial and ventricular fibrosis.

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