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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">cardiovascular</journal-id><journal-title-group><journal-title xml:lang="ru">Кардиоваскулярная терапия и профилактика</journal-title><trans-title-group xml:lang="en"><trans-title>Cardiovascular Therapy and Prevention</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1728-8800</issn><issn pub-type="epub">2619-0125</issn><publisher><publisher-name>«SILICEA-POLIGRAF» LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15829/1728-8800-2024-4088</article-id><article-id custom-type="edn" pub-id-type="custom">QLXMDS</article-id><article-id custom-type="elpub" pub-id-type="custom">cardiovascular-4088</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ЛЕГОЧНАЯ ГИПЕРТЕНЗИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>PULMONARY HYPERTENSION</subject></subj-group></article-categories><title-group><article-title>Кардиопульмональное нагрузочное тестирование у пациентов с прекапиллярной легочной гипертензией, имеющих неблагоприятный прогноз</article-title><trans-title-group xml:lang="en"><trans-title>Cardiopulmonary exercise testing in patients with precapillary pulmonary hypertension with an unfavorable prognosis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5770-3845</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Березина</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Berezina</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Аэлита Валерьевна Березина — г.н.с., руководитель НИЛ кардиопульмонального тестирования.</p><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>Saint Petersburg</p></bio><email xlink:type="simple">aelitaberezina@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1161-4430</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Злобина</surname><given-names>И. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Zlobina</surname><given-names>I. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ирина Сергеевна Злобина — врач-кардиолог.</p><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>Saint Petersburg</p></bio><email xlink:type="simple">irzlspb@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6954-7096</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гончарова</surname><given-names>Н. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Goncharova</surname><given-names>N. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Наталья Сергеевна Гончарова — к.м.н., с.н.с. НИО некоронарогенных заболеваний сердца.</p><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>Saint Petersburg</p></bio><email xlink:type="simple">ns.goncharova@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9478-1941</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Симакова</surname><given-names>М. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Simakova</surname><given-names>M. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мария Александровна Симакова — к.м.н., с.н.с. НИО некоронарогенных заболеваний сердца.</p><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>Saint Petersburg</p></bio><email xlink:type="simple">Maria.Simakova@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7337-0972</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лапшин</surname><given-names>К. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Lapshin</surname><given-names>K. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кирилл Борисович Лапшин — зав. отделением анестезиологии-реанимации с палатами реанимации и интенсивной терапии.</p><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>Saint Petersburg</p></bio><email xlink:type="simple">lapshinkb@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7817-3847</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Моисеева</surname><given-names>О. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Moiseeva</surname><given-names>O. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ольга Михайловна Моисеева — д.м.н., профессор, г.н.с., руководитель НИО некоронарогенных заболеваний сердца.</p><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>Saint Petersburg</p></bio><email xlink:type="simple">moiseeva@almazovcentre.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБУ "Национальный медицинский исследовательский центр им. В.А. Алмазова" Минздрава России</institution></aff><aff xml:lang="en"><institution>Almazov National Medical Research Center</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>23</day><month>10</month><year>2024</year></pub-date><volume>23</volume><issue>9</issue><fpage>4088</fpage><lpage>4088</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Березина А.В., Злобина И.С., Гончарова Н.С., Симакова М.А., Лапшин К.Б., Моисеева О.М., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Березина А.В., Злобина И.С., Гончарова Н.С., Симакова М.А., Лапшин К.Б., Моисеева О.М.</copyright-holder><copyright-holder xml:lang="en">Berezina A.V., Zlobina I.S., Goncharova N.S., Simakova M.A., Lapshin K.B., Moiseeva O.M.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://cardiovascular.elpub.ru/jour/article/view/4088">https://cardiovascular.elpub.ru/jour/article/view/4088</self-uri><abstract><sec><title>Цель</title><p>Цель. Провести сопоставление клинических и гемодинамических параметров с выживаемостью инцидентных больных идиопатической легочной артериальной гипертензией (ИЛАГ) и хронической тромбоэмболической легочной гипертензией (ХТЭЛГ), имеющих прогностически неблагоприятный паттерн показателей кардиопульмонального нагрузочного тестирования (КПНТ).</p></sec><sec><title>Материал и методы</title><p>Материал и методы. В исследование включены 48 инцидентных случаев с верифицированным диагнозом ИЛАГ (n=18) и ХТЭЛГ (n=30). Все пациенты обследованы в соответствии с рекомендациями Европейского общества кардиологов и Европейского респираторного общества 2015г. В качестве критерия включения выбран вентиляторный эквивалент по диоксиду углерода (СО2) по данным КПНТ (VE/VCO2) &gt;44, свидетельствующий о неблагоприятном прогнозе пациентов.</p></sec><sec><title>Результаты</title><p>Результаты. VE/VCO2 у обследованных пациентов ИЛАГ и ХТЭЛГ в среднем составил 70,6±0,8 и не различался в исследуемых группах. Гемодинамические параметры пациентов с ИЛАГ и ХТЭЛГ также указывали на высокий риск развития неблагоприятных событий: сердечный индекс 1,9±0,1 и 1,8±0,1 л/мин/м2, соответственно (р=0,3). Пиковое потребление кислорода, уровень анаэробного порога, доставка кислорода на объем выполненной работы были снижены в обеих группах. Но у пациентов с ИЛАГ отсутствовало снижение вентиляции мертвого пространства и степень десатурации при физической нагрузке была больше, чем у пациентов с ХТЭЛГ. Пациенты с ХТЭЛГ имели лучшую выживаемость по сравнению с больными ИЛАГ: 1 год — 89 vs 83%, 3 год — 84 vs 65%, 5 год — 73 vs 35%, 7 год — 55 vs 36%.</p></sec><sec><title>Заключение</title><p>Заключение. Среди пациентов с ИЛАГ и ХТЭЛГ, имеющих неблагоприятный прогноз, пациенты с ИЛАГ при физической нагрузке демонстрируют более выраженное снижение резервных возможностей сердечно-сосудистой и дыхательной систем, что негативно отражается на выживаемости пациентов. КПНТ может быть ценным неинвазивным методом стратификации риска летальных исходов у пациентов с ИЛАГ и ХТЭЛГ.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Aim</title><p>Aim. To compare clinical and hemodynamic parameters with survival of incident patients with idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) with a prognostically unfavorable pattern of cardiopulmonary exercise testing (CPET) parameters.</p></sec><sec><title>Material and methods</title><p>Material and methods. The study included 48 incident cases with a verified diagnosis of IPAH (n=18) and CTEPH (n=30). All patients were examined in accordance with the European Society of Cardiology and the European Respiratory Society guidelines (2015). The inclusion criterion was the ventilatory equivalent for carbon dioxide (CO2) according to the CPET (VE/VCO2) &gt;44, indicating an unfavorable prognosis for patients.</p></sec><sec><title>Results</title><p>Results. VE/VCO2 in the examined patients with IPAH and CTEPH averaged 70,6±0,8 and did not differ in the study groups. Hemodynamic parameters of patients with IPAH and CTEPH also indicated a high risk of adverse events as follows: cardiac index — 1,9±0,1 and 1,8±0,1 l/min/m2, respectively (p=0,3). Peak oxygen consumption, anaerobic threshold level, oxygen delivery to work performed were reduced in both groups. However, patients with IPAH did not have a decrease in dead space ventilation and desaturation severity during exercise was greater than in patients with CTEPH. Patients with CTEPH had better survival compared to patients with IPAH: 1 year — 89 vs 83%, 3 years — 84 vs 65%, 5 years — 73 vs 35%, 7 years — 55 vs 36%.</p></sec><sec><title>Conclusion</title><p>Conclusion. Among patients with IPAH and CTEPH who have an unfavorable prognosis, patients with IPAH demonstrate a more pronounced decrease in cardiovascular and respiratory reserves, which negatively affects patient survival. CPET may be a valuable non-invasive method for death risk stratification in patients with IPAH and CTEPH.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>кардиопульмональное нагрузочное тестирование</kwd><kwd>прекапиллярная легочная гипертензия</kwd><kwd>неблагоприятный прогноз</kwd></kwd-group><kwd-group xml:lang="en"><kwd>cardiopulmonary exercise testing</kwd><kwd>precapillary pulmonary hypertension</kwd><kwd>unfavorable prognosis</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование выполнено при поддержке гранта РНФ, соглашение № 23-15-00-318</funding-statement><funding-statement xml:lang="en">The study was supported by a grant from the Russian Science Foundation, agreement № 23-15-00-318</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Humbert M, Kovacs G, Hoeper MM, Badagliacca R, et al. ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2023;61:2200879. doi:10.1183/13993003.00879-2022.</mixed-citation><mixed-citation xml:lang="en">Humbert M, Kovacs G, Hoeper MM, Badagliacca R, et al. ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2023;61:2200879. doi:10.1183/13993003.00879-2022.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Легочная гипертензия. Под редакцией С. Н. Авдеева. Москва. ГЭОТАР-Медиа. 2019. 608 с. ISBN: 9785970450000.</mixed-citation><mixed-citation xml:lang="en">Pulmonary hypertension. Edited by S. N. Avdeev. Moscow. GEOTAR-Media. 2019. 608 p. (In Russ.) ISBN: 9785970450000.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Humbert M, Guignabert C, Bonnet S, et al. Pathology and patho­biology of pulmonary hypertension: state of the art and research perspectives. Eur Respir J. 2019;53:1801887. doi:10.1183/13993003.01887-2018.</mixed-citation><mixed-citation xml:lang="en">Humbert M, Guignabert C, Bonnet S, et al. Pathology and patho­biology of pulmonary hypertension: state of the art and research perspectives. Eur Respir J. 2019;53:1801887. doi:10.1183/13993003.01887-2018.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Simonneau G, Dorfmüller P, Guignabert C, et al. Chronic throm­bo­embolic pulmonary hypertension: the magic of patho­physio­logy. Ann Cardiothorac Surg. 2022;11:106-19. doi:10.21037/acs-2021-pte-10.</mixed-citation><mixed-citation xml:lang="en">Simonneau G, Dorfmüller P, Guignabert C, et al. Chronic throm­bo­embolic pulmonary hypertension: the magic of patho­physio­logy. Ann Cardiothorac Surg. 2022;11:106-19. doi:10.21037/acs-2021-pte-10.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Galiè N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019;53:1801889. doi:10.1183/13993003.01889-2018.</mixed-citation><mixed-citation xml:lang="en">Galiè N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019;53:1801889. doi:10.1183/13993003.01889-2018.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Казымлы А. В., Березина А. В., Рыжков А. В. др. Кардиопульмональное тестирование как метод оценки тяжести состояния больных с прекапиллярной легочной гипертензией. Кардиология. 2014;54(12):22-8. doi:10.18565/cardio.2014.12.22-28.</mixed-citation><mixed-citation xml:lang="en">Kyzymly AV, Berezina AV, Ryzhkov AV, et al. Cardiopulmonary Testing as a Method of Assessing Severity of Patients with Precapillary Pulmonary Hypertension. Kardiologiia. 2014;54(12): 22-8. (In Russ.) doi:10.18565/cardio.2014.12.22-28.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Симакова М. А., Злобина И. С., Березина А. В. и др. Место кардиопульмонального нагрузочного тестирования в оценке эффективности лечения пациентов с хронической тромбоэмболической легочной гипертензией. Кардиология. 2022;62:44-54. doi:10.18087/cardio.2022.4.n1611.</mixed-citation><mixed-citation xml:lang="en">Simakova MA, Zlobina IS, Berezina AV, et al. Cardiopulmonary exer­cise testing for treatment effect assessment in chronic thrombo­embolic pulmonary hypertension patients. Kardiologiia. 2022;62:44-54. (In Russ.) doi:10.18087/cardio.2022.4.n1611.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Forbes LM, Bull TM, Lahm T, et al. Exercise Testing in the Risk Assessment of Pulmonary Hypertension. Chest. 2023;164:736-46. doi:10.1016/j.chest.2023.04.013.</mixed-citation><mixed-citation xml:lang="en">Forbes LM, Bull TM, Lahm T, et al. Exercise Testing in the Risk Assessment of Pulmonary Hypertension. Chest. 2023;164:736-46. doi:10.1016/j.chest.2023.04.013.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European So­ciety of Cardiology (ESC) and the European Res­piratory So­ciety (ERS). Eur Respir J. 2015;46:903-75. doi:10.1183/13993003.51032-2015.</mixed-citation><mixed-citation xml:lang="en">2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European So­ciety of Cardiology (ESC) and the European Res­piratory So­ciety (ERS). Eur Respir J. 2015;46:903-75. doi:10.1183/13993003.51032-2015.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. European Heart Journal — Cardiovascular Imaging. 2015;16:233-71. doi:10.1093/ehjci/jev014.</mixed-citation><mixed-citation xml:lang="en">Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. European Heart Journal — Cardiovascular Imaging. 2015;16:233-71. doi:10.1093/ehjci/jev014.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Fukumitsu M, Westerhof BE, Ruigrok D, et al. Early return of reflected waves increases right ventricular wall stress in chro­nic thromboembolic pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2020;319:H1438-50. doi:10.1152/ajpheart.00442. 2020.</mixed-citation><mixed-citation xml:lang="en">Fukumitsu M, Westerhof BE, Ruigrok D, et al. Early return of reflected waves increases right ventricular wall stress in chro­nic thromboembolic pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2020;319:H1438-50. doi:10.1152/ajpheart.00442.2020.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Берези­на А. В., Козленок А. В. Кардиопульмональное тестирование в кардиологии. Трансляционная медицина. 2014;2:13-7. doi:10.18705/2311-4495-2014-0-2-105-116.</mixed-citation><mixed-citation xml:lang="en">Berezina AV, Kozlenok AV. The cardiopulmonary test in the car­diology. Translational Medicine. 2014;2:13-7. (In Russ.) doi:10.18705/2311-4495-2014-0-2-105-116.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Pezzuto B, Agostoni P. The Current Role of Cardiopulmonary Exer­cise Test in the Diagnosis and Management of Pulmonary Hyper­ten­sion. J Clin Med. 2023;12:5465. doi:10.3390/jcm12175465.</mixed-citation><mixed-citation xml:lang="en">Pezzuto B, Agostoni P. The Current Role of Cardiopulmonary Exer­cise Test in the Diagnosis and Management of Pulmonary Hyper­ten­sion. J Clin Med. 2023;12:5465. doi:10.3390/jcm12175465.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Кобелев Е., Бер­ген Т. А., Таркова А. Р. и др. COVID-19 как причина хронической легочной гипертензии: патофизиологическое обоснование и возможности инструментальной диагностики. Кардио­васкулярная терапия и профилактика. 2021;20(5):2844. doi:10.15829/1728-8800-2021-2844.</mixed-citation><mixed-citation xml:lang="en">Kobelev E, Bergen TA, Tarkova AR, et al. COVID-19 as a cause of chronic pulmonary hypertension: pathophysiological rationale and potentialof instrumental investigations. Cardiovascular The­rapy and Prevention.2021;20(5):2844. (In Russ.) doi:10.15829/1728-8800-2021-2844.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Balady J, Arena R, Sietsema K, et al. American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology. Council on Epidemiology and Prevention. Council on Peripheral Vascular Disease. Inter­disciplinary Council on Quality of Care and Outcomes Re­search. Clinician’s Guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart As­so­ciation. Circulation. 2010;122:191-225. doi:10.1161/CIR.0b013e3181e52e69.</mixed-citation><mixed-citation xml:lang="en">Balady J, Arena R, Sietsema K, et al. American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology. Council on Epidemiology and Prevention. Council on Peripheral Vascular Disease. Inter­disciplinary Council on Quality of Care and Outcomes Re­search. Clinician’s Guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart As­so­ciation. Circulation. 2010;122:191-225. doi:10.1161/CIR.0b013e3181e52e69.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
