TY - JOUR
T1 - Renal Denervation Prevents Atrial Arrhythmogenic Substrate Development in CKD
AU - Hohl, Mathias
AU - Selejan, Simina-Ramona
AU - Wintrich, Jan
AU - Lehnert, Ulrike
AU - Speer, Thimoteus
AU - Schneider, Clara
AU - Mauz, Muriel
AU - Markwirth, Philipp
AU - Wong, Dickson W L
AU - Boor, Peter
AU - Kazakov, Andrey
AU - Mollenhauer, Martin
AU - Linz, Benedikt
AU - Klinkhammer, Barbara Mara
AU - Hübner, Ulrich
AU - Ukena, Christian
AU - Moellmann, Julia
AU - Lehrke, Michael
AU - Wagenpfeil, Stefan
AU - Werner, Christian
AU - Linz, Dominik
AU - Mahfoud, Felix
AU - Böhm, Michael
PY - 2022/3/18
Y1 - 2022/3/18
N2 - BACKGROUND: In patients with chronic kidney disease (CKD), atrial fibrillation (AF) is highly prevalent and represents a major risk factor for stroke and death. CKD is associated with atrial proarrhythmic remodeling and activation of the sympathetic nervous system. Whether reduction of the sympathetic nerve activity by renal denervation (RDN) inhibits AF vulnerability in CKD is unknown.METHODS: Left atrial (LA) fibrosis was analyzed in samples from patients with AF and concomitant CKD (estimated glomerular filtration rate [eGFR], <60 mL/min per 1.73 m2) using picrosirius red and compared with AF patients without CKD and patients with sinus rhythm with and without CKD. In a translational approach, male Sprague Dawley rats were fed with 0.25% adenine (AD)-containing chow for 16 weeks to induce CKD. At week 5, AD-fed rats underwent RDN or sham operation (AD). Rats on normal chow served as control. After 16 weeks, cardiac function and AF susceptibility were assessed by echocardiography, radiotelemetry, electrophysiological mapping, and burst stimulation, respectively. LA tissue was histologically analyzed for sympathetic innervation using tyrosine hydroxylase staining, and LA fibrosis was determined using picrosirius red.RESULTS: Sirius red staining demonstrated significantly increased LA fibrosis in patients with AF+CKD compared with AF without CKD or sinus rhythm. In rats, AD demonstrated LA structural changes with enhanced sympathetic innervation compared with control. In AD, LA enlargement was associated with prolonged duration of induced AF episodes, impaired LA conduction latency, and increased absolute conduction inhomogeneity. RDN treatment improved LA remodeling and reduced LA diameter compared with sham-operated AD. Furthermore, RDN decreased AF susceptibility and ameliorated LA conduction latency and absolute conduction inhomogeneity, independent of blood pressure reduction and renal function.CONCLUSIONS: In an experimental rat model of CKD, RDN inhibited progression of atrial structural and electrophysiological remodeling. Therefore, RDN represents a potential therapeutic tool to reduce the risk of AF in CKD, independent of changes in renal function and blood pressure.
AB - BACKGROUND: In patients with chronic kidney disease (CKD), atrial fibrillation (AF) is highly prevalent and represents a major risk factor for stroke and death. CKD is associated with atrial proarrhythmic remodeling and activation of the sympathetic nervous system. Whether reduction of the sympathetic nerve activity by renal denervation (RDN) inhibits AF vulnerability in CKD is unknown.METHODS: Left atrial (LA) fibrosis was analyzed in samples from patients with AF and concomitant CKD (estimated glomerular filtration rate [eGFR], <60 mL/min per 1.73 m2) using picrosirius red and compared with AF patients without CKD and patients with sinus rhythm with and without CKD. In a translational approach, male Sprague Dawley rats were fed with 0.25% adenine (AD)-containing chow for 16 weeks to induce CKD. At week 5, AD-fed rats underwent RDN or sham operation (AD). Rats on normal chow served as control. After 16 weeks, cardiac function and AF susceptibility were assessed by echocardiography, radiotelemetry, electrophysiological mapping, and burst stimulation, respectively. LA tissue was histologically analyzed for sympathetic innervation using tyrosine hydroxylase staining, and LA fibrosis was determined using picrosirius red.RESULTS: Sirius red staining demonstrated significantly increased LA fibrosis in patients with AF+CKD compared with AF without CKD or sinus rhythm. In rats, AD demonstrated LA structural changes with enhanced sympathetic innervation compared with control. In AD, LA enlargement was associated with prolonged duration of induced AF episodes, impaired LA conduction latency, and increased absolute conduction inhomogeneity. RDN treatment improved LA remodeling and reduced LA diameter compared with sham-operated AD. Furthermore, RDN decreased AF susceptibility and ameliorated LA conduction latency and absolute conduction inhomogeneity, independent of blood pressure reduction and renal function.CONCLUSIONS: In an experimental rat model of CKD, RDN inhibited progression of atrial structural and electrophysiological remodeling. Therefore, RDN represents a potential therapeutic tool to reduce the risk of AF in CKD, independent of changes in renal function and blood pressure.
KW - ABLATION
KW - ACTIVATION
KW - CHRONIC KIDNEY-DISEASE
KW - FIBRILLATION MECHANISMS
KW - FIBROSIS
KW - HYPERTENSION
KW - INSIGHTS
KW - OVERACTIVITY
KW - PROGRESSION
KW - SYMPATHETIC DENERVATION
KW - animals
KW - atrial fibrillation
KW - chronic
KW - humans
KW - kidney failure
KW - male
KW - nervous system
KW - rats
U2 - 10.1161/circresaha.121.320104
DO - 10.1161/circresaha.121.320104
M3 - Article
C2 - 35130718
SN - 0009-7330
VL - 130
SP - 814
EP - 828
JO - Circulation Research
JF - Circulation Research
IS - 6
ER -