Felix Mahfoud1, Stefan Tunev2, Sebastian Ewen3, Bodo Cremers3, Jennifer Ruwart2, Daniel Schulz-Jander2, Dominik Linz3, Justin Davies4, David E Kandzari5, Robert Whitbourn6, Michael Böhm3, Robert J Melder2. 1. Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany. Electronic address: felix.mahfoud@uks.eu. 2. Medtronic Cardiovascular, Santa Rosa, California. 3. Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany. 4. International Centre for Circulatory Health, Imperial College London, Hammersmith Hospital, London, United Kingdom. 5. Piedmont Heart Institute, Atlanta, Georgia. 6. The Cardiovascular Research Centre, St. Vincent's Hospital Melbourne, Melbourne, Australia.
Abstract
BACKGROUND: Insufficient procedural efficacy has been proposed to explain nonresponse to renal denervation (RDN). OBJECTIVES: The aim of this study was to examine the impact of different patterns of lesion placements on the efficacy and consistency of catheter-based radiofrequency RDN in pigs. METHODS: The impact of increasing number of lesions versus location of RDN was investigated in a porcine model (Group 1; n = 51). The effect of treating the main artery, the branches, and the 2 combined was compared in Group 2 (n = 48). The durability of response and safety of combined treatment of the main artery plus branches was examined in Group 3 (n = 16). Renal norepinephrine (NE) tissue content and renal cortical axon density were assessed. RESULTS: Increasing the number of RF lesions (4, 8, and 12) in the main renal artery was not sufficient to yield a clear dose-response relationship on NE content and axon density. In contrast, targeted treatment of the renal artery branches or distal segment of the main renal artery resulted in markedly less variability of response and significantly greater reduction of both NE and axon density than conventional treatment of only the main renal artery. Combination treatment (main artery plus branches) produced the greatest change in renal NE and axon density with the least heterogeneity. The changes were durable through 28 days post-treatment. CONCLUSIONS: These data provide the rationale for investigation of an optimized approach for RDN in future clinical studies. This may have profound implications for the clinical application of RDN, as this approach may not only achieve greater reductions in sympathetic activity but also reduce treatment effect variability.
BACKGROUND: Insufficient procedural efficacy has been proposed to explain nonresponse to renal denervation (RDN). OBJECTIVES: The aim of this study was to examine the impact of different patterns of lesion placements on the efficacy and consistency of catheter-based radiofrequency RDN in pigs. METHODS: The impact of increasing number of lesions versus location of RDN was investigated in a porcine model (Group 1; n = 51). The effect of treating the main artery, the branches, and the 2 combined was compared in Group 2 (n = 48). The durability of response and safety of combined treatment of the main artery plus branches was examined in Group 3 (n = 16). Renal norepinephrine (NE) tissue content and renal cortical axon density were assessed. RESULTS: Increasing the number of RF lesions (4, 8, and 12) in the main renal artery was not sufficient to yield a clear dose-response relationship on NE content and axon density. In contrast, targeted treatment of the renal artery branches or distal segment of the main renal artery resulted in markedly less variability of response and significantly greater reduction of both NE and axon density than conventional treatment of only the main renal artery. Combination treatment (main artery plus branches) produced the greatest change in renal NE and axon density with the least heterogeneity. The changes were durable through 28 days post-treatment. CONCLUSIONS: These data provide the rationale for investigation of an optimized approach for RDN in future clinical studies. This may have profound implications for the clinical application of RDN, as this approach may not only achieve greater reductions in sympathetic activity but also reduce treatment effect variability.
Authors: Dominik Linz; Mathias Hohl; Adrian D Elliott; Dennis H Lau; Felix Mahfoud; Murray D Esler; Prashanthan Sanders; Michael Böhm Journal: Clin Auton Res Date: 2018-02-10 Impact factor: 4.435