Abraham R Tzafriri1, Felix Mahfoud2, John H Keating3, Peter M Markham3, Anna Spognardi3, Gee Wong3, Kristine Fuimaono4, Michael Böhm2, Elazer R Edelman5. 1. CBSET Inc., Lexington, Massachusetts. Electronic address: rtzafriri@cbset.org. 2. Klinik für Innere Medizin III, Kardiologie, Angiologie, und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany. 3. CBSET Inc., Lexington, Massachusetts. 4. Biosense Webster, Irwindale, California. 5. Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts; Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Abstract
BACKGROUND: Renal denervation is a new interventional approach to treat hypertension with variable results. OBJECTIVES: The purpose of this study was to correlate response to endovascular radiofrequency ablation of renal arteries with nerve and ganglia distributions. We examined how renal neural network anatomy affected treatment efficacy. METHODS: A multielectrode radiofrequency catheter (15 W/60 s) treated 8 renal arteries (group 1). Arteries and kidneys were harvested 7 days post-treatment. Renal norepinephrine (NEPI) levels were correlated with ablation zone geometries and neural injury. Nerve and ganglion distributions and sizes were quantified at discrete distances from the aorta and were compared with 16 control arteries (group 2). RESULTS: Nerve and ganglia distributions varied with distance from the aorta (p < 0.001). A total of 75% of nerves fell within a circumferential area of 9.3, 6.3, and 3.4 mm of the lumen and 0.3, 3.0, and 6.0 mm from the aorta. Efficacy (NEPI 37 ng/g) was observed in only 1 of 8 treated arteries where ablation involved all 4 quadrants, reached a depth of 9.1 mm, and affected 50% of nerves. In 7 treated arteries, NEPI levels remained at baseline values (620 to 991 ng/g), ≤20% of the nerves were affected, and the ablation areas were smaller (16.2 ± 10.9 mm(2)) and present in only 1 to 2 quadrants at maximal depths of 3.8 ± 2.7 mm. CONCLUSIONS: Renal denervation procedures that do not account for asymmetries in renal periarterial nerve and ganglia distribution may miss targets and fall below the critical threshold for effect. This phenomenon is most acute in the ostium but holds throughout the renal artery, which requires further definition.
BACKGROUND: Renal denervation is a new interventional approach to treat hypertension with variable results. OBJECTIVES: The purpose of this study was to correlate response to endovascular radiofrequency ablation of renal arteries with nerve and ganglia distributions. We examined how renal neural network anatomy affected treatment efficacy. METHODS: A multielectrode radiofrequency catheter (15 W/60 s) treated 8 renal arteries (group 1). Arteries and kidneys were harvested 7 days post-treatment. Renal norepinephrine (NEPI) levels were correlated with ablation zone geometries and neural injury. Nerve and ganglion distributions and sizes were quantified at discrete distances from the aorta and were compared with 16 control arteries (group 2). RESULTS: Nerve and ganglia distributions varied with distance from the aorta (p < 0.001). A total of 75% of nerves fell within a circumferential area of 9.3, 6.3, and 3.4 mm of the lumen and 0.3, 3.0, and 6.0 mm from the aorta. Efficacy (NEPI 37 ng/g) was observed in only 1 of 8 treated arteries where ablation involved all 4 quadrants, reached a depth of 9.1 mm, and affected 50% of nerves. In 7 treated arteries, NEPI levels remained at baseline values (620 to 991 ng/g), ≤20% of the nerves were affected, and the ablation areas were smaller (16.2 ± 10.9 mm(2)) and present in only 1 to 2 quadrants at maximal depths of 3.8 ± 2.7 mm. CONCLUSIONS: Renal denervation procedures that do not account for asymmetries in renal periarterial nerve and ganglia distribution may miss targets and fall below the critical threshold for effect. This phenomenon is most acute in the ostium but holds throughout the renal artery, which requires further definition.
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Authors: Abraham R Tzafriri; John H Keating; Peter M Markham; Anna-Maria Spognardi; James R L Stanley; Gee Wong; Brett G Zani; Debby Highsmith; Patrick O'Fallon; Kristine Fuimaono; Felix Mahfoud; Elazer R Edelman Journal: Sci Transl Med Date: 2015-04-29 Impact factor: 17.956