Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02002-5

Role of renal sympathetic nerve activation in CKD-associated cardiovascular disease and the development of malignant arrhythmias -A pilot study -
M. Hohl1, S.-R. Selejan1, J. Wintrich1, A. Schulz1, J. Hönig1, T. Speer2, F. Mahfoud1, M. Böhm1
1Innere Medizin III - Kardiologie, Angiologie und internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar; 2Nephrologie, Klinik für Innere Medizin IV, Homburg/Saar;
Background: Chronic kidney disease (CKD) is associated with hypertension and subsequent cardiovascular comorbidities. Both, CKD and hypertension associate with an activation of the sympathetic nervous system (SNS), which may cause cardiac structural and electrophysiological remodeling predisposing to the occurrence of atrial fibrillation (AF). We investigated the interplay between kidney failure, SNS activity and AF inducibility in a rat model with CKD and hypertension. Moreover, we assessed whether renal denervation (RDN) helps to prevent AF arrhythmogenesis.

Methods: At an age of 20 weeks, eight male Spontaneously Hypertensive Rats (SHR) were fed with 0.25% adenine-containing diet (AD) for 16 weeks to induce CKD. As control, four SHR received standard diet (Ctrl). At week five, AD rats were subjected to bilateral surgical RDN (AD-RDN; n=4), or sham surgery (AD-Sham; n=4, Ctrl-Sham; n=4). Serum urea and creatinine levels were measured to assess kidney function. Development of mean arterial pressure (MAP) was documented by radio-telemetry. Left ventricular (LV) and left atrial (LA) dimension and function were assessed by echocardiography. After 16 weeks, cardiac electrical alterations were investigated by ECG-evaluation and epicardial mapping.

Results: After 16 weeks, adenine-intake resulted in significant increased serum urea and creatinine levels compared with Ctrl, indicating impaired renal function. RDN did not affect kidney function. Heart weight/tibia length (Ctrl-Sham: 312.5±37.3 mg/cm, AD-Sham: 318.8±12.5 mg/cm; AD-RDN: 311.1±6.5 mg/cm) and elevation of MAP over time (D 16 weeks to baseline) was comparable between all groups (Ctrl-Sham: 18.75±5.4 mmHg, AD-Sham: 18.53±1.4 mmHg; AD-RDN: 23.21±2.8 mmHg). Echocardiography revealed increased LV wall thickness (LV posterior wall, LVPW) in AD-Sham compared to Ctrl-Sham (2.78±0.17 mm vs. 2.38±0.05 mm, p=0.10) and increased LA diameter (4.46±0.07 mm vs. 4.23±0.03 mm, p=0.075). In AD-RDN, LVPW (2.50±0.1 mm, p=0.22 vs. AD-Sham), and LA diameter (4.32±0.07 mm, p=0.27 vs. AD-Sham) were numerically decreased compared to AD-Sham. P-wave duration was prolonged in AD-Sham compared with Ctrl-Sham (29.6±1.9 ms vs. 25.7±0.7 ms, p=0.10) and was attenuated by RDN (26.9±0.4 ms, p=0.30 vs. AD-Sham). Epicardial mapping demonstrated increased atrial conduction latency in AD-Sham (1.05±0.25 s/m vs. 0.72±0.06 s/m; p=0.25 vs. Ctrl-Sham) and atrial absolute inhomogeneity (3.52±0.86 P5/P95 vs. 2.64±0.64 P5/P95, p=0.47 vs. Ctrl-Sham). RDN led to a numerical, albeit non-significant decrease in (1.00±0.10 s/m; p=0.86 vs AD-Sham) and absolute inhomogeneity (3.07±0.37 P5/P95, p=0.64 vs. AD-Sham).
 
Conclusion: In a hypertensive rat model with concomitant CKD the development of an arrhythmogenic substrate in the left atrium was accelerated by CKD. RDN performed after five weeks of continued adenine diet weakened the progression of a LA pro-arrhythmic remodeling and LV hypertrophy without affecting kidney function or MAP reduction.

https://dgk.org/kongress_programme/jt2022/aP493.html