BACKGROUND: Although ∼20% of the elderly population develops atrial fibrillation (AF), little is known about the mechanisms. Heart failure with preserved ejection fraction (HFpEF), which is associated with AF, is more common in aged women than in men. OBJECTIVE: The purpose of this study was to identify potential mechanisms of AF in an age-related HFpEF model. METHODS: In aged female Fischer F344 rats (21- to 24-month-old), which are prone to HFpEF, we induced AF by atrial pacing. Young Fischer F344 female rats (3- to 4-month-old) and age-matched Sprague Dawley female rats (27-month-old) served as controls. Phenotyping included echocardiography to assess left ventricular structure/function; in vivo electrophysiology and ex vivo high-resolution optical mapping to assess AF vulnerability; systemic and atrial inflammatory profiling; atrial histology; and expression of inflammasome signaling proteins. RESULTS: Aged rats developed left ventricular hypertrophy, left atrial enlargement, diastolic dysfunction, and pulmonary congestion, without ejection fraction impairment, thus meeting the criteria for HFpEF. Increased serum inflammatory markers, hypertension, and obesity further characterize aged females. Sinoatrial and atrioventricular node dysfunction was associated with the high inducibility of AF in aged rats. Ex vivo electrical activation mapping revealed abnormal β-adrenergic responsiveness and slowed conduction velocity. Atrial inflammasome signaling was enhanced in aged rats, which may contribute to fibrotic remodeling and high AF susceptibility. CONCLUSION: Together, our data demonstrate that aging-related atrial remodeling and HFpEF are associated with atrial enlargement, fibrosis, conduction abnormalities, and nodal dysfunction, favoring a substrate conducive to AF.
BACKGROUND: Although ∼20% of the elderly population develops atrial fibrillation (AF), little is known about the mechanisms. Heart failure with preserved ejection fraction (HFpEF), which is associated with AF, is more common in aged women than in men. OBJECTIVE: The purpose of this study was to identify potential mechanisms of AF in an age-related HFpEF model. METHODS: In aged female Fischer F344 rats (21- to 24-month-old), which are prone to HFpEF, we induced AF by atrial pacing. Young Fischer F344 female rats (3- to 4-month-old) and age-matched Sprague Dawley female rats (27-month-old) served as controls. Phenotyping included echocardiography to assess left ventricular structure/function; in vivo electrophysiology and ex vivo high-resolution optical mapping to assess AF vulnerability; systemic and atrial inflammatory profiling; atrial histology; and expression of inflammasome signaling proteins. RESULTS: Aged rats developed left ventricular hypertrophy, left atrial enlargement, diastolic dysfunction, and pulmonary congestion, without ejection fraction impairment, thus meeting the criteria for HFpEF. Increased serum inflammatory markers, hypertension, and obesity further characterize aged females. Sinoatrial and atrioventricular node dysfunction was associated with the high inducibility of AF in aged rats. Ex vivo electrical activation mapping revealed abnormal β-adrenergic responsiveness and slowed conduction velocity. Atrial inflammasome signaling was enhanced in aged rats, which may contribute to fibrotic remodeling and high AF susceptibility. CONCLUSION: Together, our data demonstrate that aging-related atrial remodeling and HFpEF are associated with atrial enlargement, fibrosis, conduction abnormalities, and nodal dysfunction, favoring a substrate conducive to AF.
Authors: Dirk Westermann; Diana Lindner; Mario Kasner; Christine Zietsch; K Savvatis; F Escher; J von Schlippenbach; C Skurk; Paul Steendijk; Alexander Riad; Wolfgang Poller; Heinz-Peter Schultheiss; Carsten Tschöpe Journal: Circ Heart Fail Date: 2010-11-12 Impact factor: 8.790
Authors: Frederick A Masoudi; Edward P Havranek; Grace Smith; Ronald H Fish; John F Steiner; Diana L Ordin; Harlan M Krumholz Journal: J Am Coll Cardiol Date: 2003-01-15 Impact factor: 24.094
Authors: T Scott Bowen; Dominic Brauer; Natale P L Rolim; Fredrik H Bækkerud; Angela Kricke; Anne-Marie Ormbostad Berre; Tina Fischer; Axel Linke; Gustavo Justo da Silva; Ulrik Wisloff; Volker Adams Journal: J Am Heart Assoc Date: 2017-10-24 Impact factor: 5.501
Authors: Maarten Hulsmans; Hendrik B Sager; Jason D Roh; María Valero-Muñoz; Nicholas E Houstis; Yoshiko Iwamoto; Yuan Sun; Richard M Wilson; Gregory Wojtkiewicz; Benoit Tricot; Michael T Osborne; Judy Hung; Claudio Vinegoni; Kamila Naxerova; David E Sosnovik; Michael R Zile; Amy D Bradshaw; Ronglih Liao; Ahmed Tawakol; Ralph Weissleder; Anthony Rosenzweig; Filip K Swirski; Flora Sam; Matthias Nahrendorf Journal: J Exp Med Date: 2018-01-16 Impact factor: 14.307
Authors: Jonathan P Ariyaratnam; Adrian D Elliott; Ricardo S Mishima; Celine Gallagher; Dennis H Lau; Prashanthan Sanders Journal: Heart Rhythm O2 Date: 2021-12-17
Authors: Max J Cumberland; Leto L Riebel; Ashwin Roy; Christopher O'Shea; Andrew P Holmes; Chris Denning; Paulus Kirchhof; Blanca Rodriguez; Katja Gehmlich Journal: Front Physiol Date: 2022-02-07 Impact factor: 4.566