Histological Justification for the Need of Radiofrequency Ablation of Pulmonary Arteries in Patients with High-Grade Secondary Pulmonary Hypertension

The aim of the study was to perform a histological assessment of the effectiveness of radiofrequency exposure for circular denervation of the pulmonary artery in patients with secondary high pulmonary hypertension.

Materials and Methods. The study was carried out on the autopsy material derived from non-operated patients. Three groups were formed. The experimental group included the material (207 histological samples) from the patients with chronic high pulmonary hypertension arising on the background of mitral heart disease. The samples of this group were exposed to circular radiofrequency ablation. In the comparison group, we used autopsy material (24 samples) obtained from the patients with high pulmonary hypertension. The control group included material (35 samples) from the patients without pulmonary hypertension who died from causes not associated with cardiovascular diseases. The samples of the comparison and control groups were not exposed to radiofrequency.

Visual evaluation of the damage to the vascular wall was performed after hematoxylin and eosin staining, according to Van Gieson. Damage to the nerve plexuses was evaluated after their impregnation by silver salts. To assess the degree of damage to the vascular wall on the stained sections, a scoring method of semi-quantitative analysis of the observed pathological processes (fibrinoid necrosis, metachromasia, karyorrhexis, karyolysis, fibrinoid and mucoid swelling, lipid presence) was used. Silver salt impregnation allowed visualizing damage to the reticular fibers, trunks and endings of peripheral nerve fibers.

Results. The mean optical density of the ablation group was statistically significantly lower than in the comparison and control groups (p<0.001). The mean specific area of tissue dissociation was higher in the “marginal zones” of the ablated sections, under pronounced mechanical compression in these areas. The difference in the mean areas of the argentophilic samples of the ablation and comparison and control groups was expressed in a lower percentage of argentophilic fibrous structures (p<0.05). At the same time, the highest concentration of argentophilic structures was observed in the comparison group, which points to a bigger content of nerve fiber structures in the patients with high pulmonary hypertension.

Conclusion. The results of the histological study demonstrated the feasibility of radiofrequency ablation of the pulmonary arteries in patients with high-grade secondary pulmonary hypertension. Radiofrequency denervation leads to the destruction of the sympathetic ganglia in the adventitial layer of the pulmonary arteries, which are responsible for the spasm of the precapillary bed of the pulmonary circulation, which promotes vasodilation, an increase in the vascular bed, and, as a result, a reduction in pulmonary hypertension.

1. Hayek E., Gring C.N., Griffin B.P. Mitral valve prolapse. Lancet 2005; 365(9458): 507–518, https://doi.org/10.1016/S0140-6736(05)17869-6.
2. Trofimov N.A., Medvedev A.P., Dragunov A.G., Babokin V.E., Nikol’skiy A.V., Mizurova T.N., Gartfelder M.V., Orlova A.V. Denervation of pulmonary trunk and pulmonary orifice in patients with surgically corrected mitral valve disease against high pulmonary hypertension. Al’manah kliniceskoj mediciny 2017; 45(3): 192–199, https://doi.org/10.18786/2072-0505-2017-45-3-192-199.
3. Bockeria L.A., Klimchuk I.Ya. Mitral regurgitationin patients with atrial fibrillation. Current state of the problem, approaches to diagnosis and complex surgical treatment. Annaly aritmologii 2015; 12(4): 201–214, https://doi.org/10.15275/annaritmol.2015.4.2.
4. Medvedev A.P., Skopin I.I., Chiginev V.A., Trofimov N.A., Fedorov S.A., Zhil’tsov D.D., Zemskova E.N. Key aspects of the development of modern valve cardiac surgery. Medicinskij al’manah 2015; 3: 32–37.
5. Bockeria L.A., Shengelia L.D. Treatment of atrial fibrillation. Part II. Current realities and future prospects. Annaly aritmologii 2014; 11(2): 76–86.
6. Babokin V.E., Trofimov N.A. Prevention of atrial fibrillation recurrence after the maze IV procedure. Ann Thorac Surg 2019; 109(5): 1624–1625, https://doi.org/10.1016/j.athoracsur.2019.08.087.
7. Vaskovskiy V.A., Serguladze S.Yu. Possibilities and prospects of surgical treatment of atrial fibrillation. Annaly aritmologii 2016; 13(2): 64–72.
8. Sulimov V.A., Lishuta A.S. Prospects for the treatment of patients with atrial fibrillation. Racionalʹnaa farmakoterapia v kardiologii 2011; 7(3): 323–333.
9. Zheleznev S.I., Demidov D.P., Afanasiev A.V., Nazarov V.M., Demin I.I., Bogachev-Prokofiev A.V., Astapov D.A., Karaskov A.M. Radiofrequency denervation of pulmonary artery in surgery of dysplastic mitral valve defects with severe pulmonary hypertension. Rossijskij kardiologicheskij zhurnal 2016; 11: 70–72, https://doi.org/10.15829/1560-4071-2016-11-70-72.
10. Trofimov N.A., Medvedev A.P., Babokin V.E., Dragunov A.G., Efimova I.P., Gartfelder M.V., Nikolaeva O.V., Dragunova M.V., Sozykin A.V., Averin E.E., Shlykov A.V., Novikova N.T. Effectiveness of PADN-procedure in patients with high pulmonary hypertension against background of mitral valve dysfunction complicated by atrial fibrillation and effect on preservation of sinus rhythm in postoperative period. Medicinskij alfavit 2018; 4: 18–24.
11. Porodenko N.V., Skibitskiy V.V., Zapevina V.V. The diagnosis and treatment of primary pulmonary hypertension: a modern view on the problem. Kubanskij nauchnyj meditsinskij vestnik 2014; 3: 140–144.
12. Rubin L.J. Primary pulmonary hypertension. N Eng J Med 1997; 336(2): 111–117, https://doi.org/10.1056/nejm199701093360207.
13. Gaine S. Pulmonary hypertension. JAMA 2000; 284(24): 3160–3168, https://doi.org/10.1001/jama.284.24.3160.
14. Simonneau G., Montani D., Celermajer D.S., Denton C.P., Gatzoulis M.A., Krowka M., Williams P.G., Souza R. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J 2019; 53(1): 1801913, https://doi.org/10.1183/13993003.01913-2018.
15. Guazzi M., Vitelli A., Labate V., Arena R. Treatment for pulmonary hypertension of left heart disease. Curr Treat Options Cardiovasc Med 2012; 14(4): 319–327, https://doi.org/10.1007/s11936-012-0185-6.
16. Chen S.L., Zhang F.F., Xu J., Xie D.J., Zhou L., Nguyen T., Stone G.W. Pulmonary artery denervation to treat pulmonary arterial hypertension: the single-center, prospective, first-in-man PADN-1 study (first-in-man pulmonary artery denervation for treatment of pulmonary artery hypertension). J Am Coll Cardiol 2013; 62(12): 1092–1100, https://doi.org/10.1016/j.jacc.2013.05.075.
17. Bogachev-Prokof’ev A.V., Zheleznev S.I., Afanas’ev A.V., Fomenko M.S., Demidov D.P., Sharifulin R.M., Pivkin A.N., Astapov D.A., Semenova E.I., Ivanov S.N., Karas’kov A.M. Denervation of pulmonary artery during mitral valve surgery in patients with high pulmonary hypertension. Patologiya krovoobrashcheniya i kardiokhirurgiya 2016; 19(4): 19–25.
18. Trofimov N.A., Medvedev A.P., Dragunov A.G., Mizurova T.N., Zhamlikhanov N.D., Nikolskij A.V., Gartfelder M.V., Dragunova M.V., Nikolaeva O.V. Method of surgical treatment of secondary pulmonary hypertension in patients with mitral valve defects. 2018. Patent RU 2661710.
19. Allred D.C., Harvey J.M., Berardo M., Clark G.M. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 1998; 11(2): 155–168.
20. Constantine A., Dimopoulos K. Pulmonary artery denervation for pulmonary arterial hypertension. Trends Cardiovasc Med 2021; 31(4): 252–260, https://doi.org/10.1016/j.tcm.2020.04.005.

Trofimov N.A., Rodionov A.L., Egorov D.V., Surkova T.V., Nikolsky A.V. Histological Justification for the Need of Radiofrequency Ablation of Pulmonary Arteries in Patients with High-Grade Secondary Pulmonary Hypertension. Sovremennye tehnologii v medicine 2021; 13(6): 56, https://doi.org/10.17691/stm2021.13.6.06