Các thiết bị theo dõi huyết động học cấy ghép để hướng dẫn điều trị suy tim: tổng quan và phân tích tổng hợp các thử nghiệm ngẫu nhiên

Clinical Research in Cardiology - Tập 112 - Trang 1007-1019 - 2022
Antonio Iaconelli1,2, Pierpaolo Pellicori1, Elisabetta Caiazzo3,4, Asma O. M. Rezig3, Dario Bruzzese5, Pasquale Maffia3,4, John G. F. Cleland1
1School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK
2Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
3School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
4Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
5Department of Public Health, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy

Tóm tắt

Tắc nghẽn là yếu tố chính dẫn đến tình trạng bệnh tật và tử vong trong suy tim. Các thiết bị theo dõi huyết động học cấy ghép có thể cho phép xác định sớm và quản lý tắc nghẽn. Bài báo này cung cấp một tổng quan hiện trạng về các thiết bị theo dõi huyết động học cấy ghép cho bệnh nhân suy tim, bao gồm một phân tích tổng hợp các thử nghiệm ngẫu nhiên. Chúng tôi đã thực hiện một tìm kiếm hệ thống cho các thử nghiệm đã công bố hoặc đang chờ công bố trong Medline, Embase, và Cơ sở Dữ liệu Thử nghiệm Có Kiểm soát của Cochrane (CENTRAL) vào ngày 22 tháng 9 năm 2021. Chúng tôi đã đưa vào các thử nghiệm ngẫu nhiên so sánh quản lý với hoặc không có thông tin từ các thiết bị theo dõi huyết động học cấy ghép cho bệnh nhân suy tim. Các kết quả được chọn bao gồm nhập viện do suy tim và tử vong do tất cả các nguyên nhân. Những thay đổi trong điều trị liên quan đến theo dõi huyết động đã chỉ dẫn đến một sự giảm nhẹ áp lực động mạch phổi trung bình (thường < 1 mmHg như là trung bình hàng ngày), mà thường vẫn lớn hơn 20 mmHg. Theo dõi huyết động đã giúp giảm tỷ lệ nhập viện do suy tim (HR 0.75; 95% CI 0.58–0.96; p = 0.03) nhưng không làm giảm tỷ lệ tử vong (RR 0.92; 95% CI 0.68–1.26; p = 0.48). Việc theo dõi huyết động cho bệnh nhân suy tim có thể làm giảm nguy cơ nhập viện do suy tim nhưng điều này vẫn chưa được chuyển thành giảm tỷ lệ tử vong, có thể do thời gian của các thử nghiệm quá ngắn hoặc việc giảm áp lực động mạch phổi không đủ lớn. Hiệu quả và độ an toàn của việc nhắm tới các giảm nhẹ lớn hơn trong áp lực động mạch phổi nên được khám phá.

Từ khóa

#suy tim #thiết bị theo dõi huyết động học #phân tích tổng hợp #nhập viện #tử vong

Tài liệu tham khảo

Pellicori P, Cleland JG, Zhang J, Kallvikbacka-Bennett A, Urbinati A, Shah P et al (2016) Cardiac dysfunction, congestion and loop diuretics: their relationship to prognosis in heart failure. Cardiovasc Drugs Ther 6:599–609. https://doi.org/10.1007/s10557-016-6697-7 Gheorghiade M, Follath F, Ponikowski P, Barsuk JH, Blair JEA, Cleland JG et al (2010) Assessing and grading congestion in acute heart failure: a scientific statement from the acute heart failure committee of the heart failure association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine. Eur J Heart Fail 12:423–433. https://doi.org/10.1093/eurjhf/hfq045 Felker GM, Anstrom KJ, Adams KF, Ezekowitz JA, Fiuzat M, Houston-Miller N et al (2017) Effect of natriuretic peptide-guided therapy on hospitalization or cardiovascular mortality in high-risk patients with heart failure and reduced ejection fraction: a randomized clinical trial. JAMA 318:713–720. https://doi.org/10.1001/jama.2017.10565 Maisel A, Barnard D, Jaski B, Frivold G, Marais J, Azer M et al (2013) Primary results of the HABIT trial (heart failure assessment with BNP in the home). J Am Coll Cardiol 61(16):1726–1735. https://doi.org/10.1016/j.jacc.2013.01.052 (Epub 2013 Mar 26. PMID: 23500322) Massari F, Scicchitano P, Iacoviello M, Passantino A, Guida P, Sanasi M et al (2019) Multiparametric approach to congestion for predicting long-term survival in heart failure. J Cardiol 75:47–52. https://doi.org/10.1016/j.jjcc.2019.05.017 Damy T, Goode KM, Kallvikbacka-Bennett A, Lewinter C, Hobkirk J, Nikitin NP et al (2010) Determinants and prognostic value of pulmonary arterial pressure in patients with chronic heart failure. Eur Heart J 31:2280–2290. https://doi.org/10.1093/eurheartj/ehq245 Braunschweig F, Linde C, Eriksson MJ, Hofman-Bang C, Rydén L (2002) Continuous hemodynamic monitoring during withdrawal of diuretics in patients with congestive heart failure. Eur Heart J 23:59–69. https://doi.org/10.1053/euhj.2001.2690 Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M et al (2022) ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. https://doi.org/10.1183/13993003.00879-2022 Kovacs G, Berghold A, Scheidl S, Olschewski H (2009) Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J 34:888–894. https://doi.org/10.1183/09031936.00145608 Maron BA, Hess E, Maddox TM, Opotowsky AR, Tedford RJ, Lahm T et al (2016) Association of borderline pulmonary hypertension with mortality and hospitalization in a large patients cohort: insights from the VA-CART program. Circulation 13:1240–1248. https://doi.org/10.1161/CIRCULATIONAHA.115.020207 Augustine DX, Coates-Bradshaw LD, Willis J, Harkness A, Ring L, Grapsa J et al (2018) Echocardiographic assessment of pulmonary hypertension: a guideline protocol from the British Society of Echocardiography. Echo Res Pract 3:11–24. https://doi.org/10.1530/ERP-17-0071 Greiner S, Jud A, Aurich M, Hess A, Hilbel T, Hardt S et al (2014) Reliability of non invasive assessment of systolic pulmonary artery pressure by Doppler echocardiography compared to right heart catheterization: analysis in a large patient population. J Am Heart Assoc Cardiovasc Cerebrovasc Dis 3:e001103. https://doi.org/10.1161/JAHA.114.001103 Zile MR, Bennett TD, Sutton MJ, Cho YK, Adamson PB, Aaron MF et al (2008) Transition from chronic compensated to acute decompensated heart failure: pathophysiological insights obtained from continuous monitoring of intracardiac pressures. Circulation 118:1433–1441. https://doi.org/10.1161/CIRCULATIONAHA.108.783910 Assad TR, Hemnes AR, Larkin EK, Glazer AM, Xu M, Wells QS et al (2016) Clinical and biological insights into combined post- and pre-capillary pulmonary hypertension. J Am Coll Cardiol. 68(23):2525–2536. https://doi.org/10.1016/j.jacc.2016.09.942 (PMID: 27931609; PMCID: PMC5157701) Al-Omary MS, Sugito S, Boyle AJ, Sverdlov AL, Collins NJ (2020) Pulmonary hypertension due to left heart disease: diagnosis, pathophysiology, and therapy. Hypertension 75(6):1397–1408. https://doi.org/10.1161/HYPERTENSIONAHA.119.14330 (Epub 2020 Apr 27, PMID: 32336230) Damy T, Hobkirk J, Walters M, Ciobanu A, Rigby AS, Kallvikbacka-Bennett A et al (2015) Development of a human model for the study of effects of hypoxia, exercise, and sildenafil on cardiac and vascular function in chronic heart failure. J Cardiovasc Pharmacol 66(3):229–238. https://doi.org/10.1097/FJC.0000000000000262 (PMID: 25874853) Guazzi M, Naeije R (2017) Pulmonary hypertension in heart failure: pathophysiology, pathobiology, and emerging clinical perspectives. J Am Coll Card 69:1718–1734. https://doi.org/10.1016/j.jacc.2017.01.051 Maron BA, Kovasc G, Vaidya A, Bhatt DL, Nishimura RA, Mak S et al (2020) Cardiopulmonary hemodynamic in pulmonary hypertension and heart failure. J Am Coll Card 22:2671–2681. https://doi.org/10.1016/j.jacc.2020.10.007 Shah AM, Shah SJ, Anand IS, Sweitzer NK, O’Meara E, Heitner JF et al (2014) Cardiac structure and function in hear failure with preserved ejection fraction: baseline findings from the echocardiographic study of the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial. Circ Heart Fail 7:104–115. https://doi.org/10.1016/j.jacc.2016.07.763 Miller WL, Grill DE, Borlaug BA (2013) Clinical features, hemodynamics, and outcomes of pulmonary hypertension due to chronic heart failure with reduced ejection fraction. JACC Heart Fail 1:290–299. https://doi.org/10.1016/j.jchf.2013.05.001 Zile MR, Gottdiener JS, Hetzel SJ, McMurray JJ, Komajda M, McKelvie R et al (2011) Prevalence and significance of alterations in cardiac structure and function in patients with heart failure and a preserved ejection fraction. Circulation 124:2491–2501. https://doi.org/10.1161/CIRCULATIONAHA.110.011031 Damy T, Kallvikbacka-Bennett A, Goode K, Khaleva O, Lewinter C, Hobkirk J et al (2012) Prevalence of, associations with, and prognostic value of tricuspid annular plane systolic excursion (TAPSE) among out-patients referred for the evaluation of heart failure. J Card Fail 18:216–225. https://doi.org/10.1016/j.cardfail.2011.12.003 Leung CC, Moondra V, Catherwood E, Andrus BW (2010) Prevalence and risk factors of pulmonary hypertension in patients with elevated pulmonary venous pressure and preserved ejection fraction. Am J Cardiol 206:284–286. https://doi.org/10.1016/j.amjcard.2010.02.039 Gorter TM, Hoendermis ES, Veldhuisen DJ, Voors AA, Lam CSP, Geelhoed B et al (2016) Right ventricular dysfunction in heart failure with preserved ejection fraction: a systematic review and meta-analysis. Eur J Heart Fail 18:1472–1487. https://doi.org/10.1002/ejhf.630 Aronson D, Darawsha W, Atamna A, Kaplan M, Makhoul BF, Mutlak D et al (2013) Pulmonary hypertension, right ventricular function, and clinical outcome in acute decompensated heart failure. J Card Fail 19:665–671. https://doi.org/10.1016/j.cardfail.2013.08.007 Ghio S, Gavazzi A, Campana C, Inserra C, Klersy C, Sebastiani R et al (2001) Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Card 37:183–188. https://doi.org/10.1016/s0735-1097(00)01102-5 Borlaug BA, Blair J, Bergmann M, Bugger H, Burkhoff D, Bruch L et al (2022) Latent pulmonary vascular disease fundamentally alters the response to therapeutic atrial shunt device in heart failure. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.122.059486 Wolsk E, Kaye DM, Komtebedde J, Shah SJ, Borlaug BA, Burkhoff D et al (2021) Determinants and consequences of heart rate and stroke volume response to exercise in patients with heart failure and preserved ejection fraction. Eur J Heart Fail 23:754–764. https://doi.org/10.1002/ejhf.2146 Lam CSP, Roger VL, Rodeheffer RJ, Borlaug BA, Enders FT, Redfiel MM (2009) Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study. J Am Coll Card 13:1119–1126. https://doi.org/10.1016/j.jacc.2008.11.051 Binanay C, Califf RM, Hasselblad V, O’Connor CM, Shah MR, Sopko G et al (2005) ESCAPE investigators and ESCAPE study coordinators evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial. JAMA 294:1625–1633. https://doi.org/10.1001/jama.294.13.1625 Shah MR, Hasselblad V, Stevenson LW, Binanay C, O’Connor CM, Sopko G et al (2005) Impact of the pulmonary artery catheter in critically ill patients: meta-analysis of randomized clinical trials. JAMA 294(13):1664–1670. https://doi.org/10.1001/jama.294.13.1664 (PMID: 16204666) Magalski A, Adamson P, Gadler F, Böehm M, Steinhaus D, Reynolds D et al (2002) Continuous ambulatory right heart pressure measurements with an implantable hemodynamic monitor: a multicentre 12-months follow up study of patients with chronic heart failure. J Card Fail 8:63–70. https://doi.org/10.1054/jcaf.2002.32373 Adamson PB, Conti JB, Smith AL, Abraham WT, Aaron MF, Aranda JM et al (2022) Reducing events in patients with chronic heart failure study design: continuous hemodynamic monitor with an implantable defibrillator. Clin Cardiol 30:567–575. https://doi.org/10.1002/clc.20250 Angermann CE, Assmus B, Anker SD, Brachmann J, Ertl G, Kohler F et al (2018) Safety and feasibility of pulmonary artery pressure-guided heart failure therapy: rationale and design of prospective CardioMEMS Monitoring Study for Heart Failure (MEMS-HF). Clin Res Cardiol 107:991–1002. https://doi.org/10.1007/s00392-018-1281-8 McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, ESC Scientific Document Group 2021 et al (2021) 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 42:3599–3726. https://doi.org/10.1093/eurheartj/ehab368 Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM et al (2022) 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. https://doi.org/10.1161/CIR.0000000000001063 (Epub ahead of print. PMID: 35363499) Lindenfeld J, Zile MR, Desai AS, Bhatt K, Ducharme A, Horstmanshof D et al (2021) Haemodynamic-guided management of heart failure (GUIDE-HF): a randomised controlled trial. Lancet 398:991–1001. https://doi.org/10.1016/S0140-6736(21)01754-2 Abraham WT, Adamson PB, Bourge RC, Aaron MF, Costanzo MR, Stevenson LW, CHAMPION Trial Study Group et al (2011) Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial. Lancet 377:658–666. https://doi.org/10.1016/S0140-6736(11)60101-3 Abraham WT, Stevenson LW, Bourge RC, Lindenfeld JA, Bauman JG, Adamson PB (2016) Sustained efficacy of pulmonary artery pressure to guide adjustment of chronic heart failure therapy: complete follow-up results from the CHAMPION randomised trial. Lancet 387:453–461. https://doi.org/10.1016/S0140-6736(15)00723-0 Givertz MM, Stevenson LW, Costanzo MR, Bourge RC, Bauman JG, Ginn G et al (2017) Pulmonary artery pressure-guided management of patients with heart failure and reduced ejection fraction. J Am Coll Cardiol 70:1875–1886. https://doi.org/10.1016/j.jacc.2017.08.010 Adamson PB, Abraham WT, Bourge RC, Costanzo MR, Hasan A, Yadav C et al (2014) Wireless pulmonary artery pressure monitoring guides management to reduce decompensation in heart failure with preserved ejection fraction. Circ Heart Fail 7:935–944. https://doi.org/10.1161/CIRCHEARTFAILURE.113.001229 Bourge RC, Abraham WT, Adamson PB, Aaron MF, Aranda JM Jr, Magalski A, COMPASS-HF Study Group et al (2008) Randomized controlled trial of an implantable continuous hemodynamic monitor in patients with advanced heart failure. J Am Coll Card 51:1073–1079. https://doi.org/10.1016/j.jacc.2007.10.061 Zile MR, Bourge RC, Bennet TD, Stevenson LW, Cho YK, Adamson PB et al (2008) Application of implantable hemodynamic monitoring in the management of patients with diastolic heart failure: a subgroup analysis of the COMPASS-HF trial. J Card Fail 14:816–823. https://doi.org/10.1016/j.cardfail.2008.07.235 Adamson PB, Gold MR, Bennett T, Bourge RC, Stevenson LW, Trupp R et al (2011) Continuous hemodynamic monitoring in patients with mild to moderate heart failure: results of the reducing decompensation events utilizing intracardiac pressures in patients with chronic heart failure (REDUCEhf) trial. Congest Heart Fail 17:248–254. https://doi.org/10.1111/j.1751-7133.2011.00247 Cleland JGF, Pellicori P (2021) To master heart failure, first master congestion. Lancet 398:935–936. https://doi.org/10.1016/S0140-6736(21)01914-0 Cowie MR, Cleland JGF (2022) The COVID-19 pandemic and heart failure: lessons from GUIDE-HF. Eur Heart J 43(27):2619–2621. https://doi.org/10.1093/eurheartj/ehac226 (PMID: 35511076, PMCID: PMC9279113) Zile MR, Bennett TD, El Hajj S, Kueffer FJ, Baicu CF, Abraham WT et al (2017) Intracardiac pressures measured using an implantable hemodynamic monitor. Relationship to mortality in patients with chronic heart failure. Circ Heart Fail 10:e003594. https://doi.org/10.1161/CIRCHEARTFAILURE.116.003594 Magalski A, Adamson P, Gadler F, Böehm M, Steinhaus D, Reynolds D et al (2002) Continuous ambulatory right heart pressure measurements with an implantable hemodynamic monitor: a multicenter, 12-month follow-up study of patients with chronic heart failure. J Card Fail 8:63–70. https://doi.org/10.1054/jcaf.2002.32373 Adamson PB, Magalski A, Braunschweig F, Böhm M, Reynolds D, Steinhaus D et al (2003) Ongoing right ventricular hemodynamics in heart failure: clinical value of measurements derived from an implantable monitoring system. J Am Coll Cardiol 41:565–571. https://doi.org/10.1016/s0735-1097(02)02896-6 Cleland JGF, Renjit A (2011) It makes SENSE to take a safer road. Eur Heart J 32:2225–2227. https://doi.org/10.1093/eurheartj/ehr120 Zile MR, Desai AS, Costanzo MR, Ducharme A, Maisel A, Mehra MR et al (2022) The GUIDE-HF trial of pulmonary artery pressure monitoring in heart failure: impact of the COVID-19 pandemic. Eur Heart J. https://doi.org/10.1093/eurheartj/ehac114 (Epub ahead of print. PMID: 35266003) Mamazhakypov A, Hein L, Lother A (2021) Mineral receptors in pulmonary hypertension and right heart failure: from molecular biology to therapeutic targeting. Pharmacol Ther 1:107987. https://doi.org/10.1016/j.pharmthera.2021.107987 Tran JS, Havakuk O, McLeod JM, Hwang J, Kwong HY, Shavelle D et al (2021) Acute pulmonary pressure change after transition to sacubitril/valsartan in patients with heart failure reduced ejection fraction. ESC Heart Fail 8:1706–1710. https://doi.org/10.1002/ehf2.13225 Khan Z, Gholkar G, Tolia S, Cadeau H, Zughaib M (2018) Effect of sacubitril/valsartan on cardiac filling pressures in patients with left ventricular systolic dysfunction. Int J Card 271:169–173. https://doi.org/10.1016/j.ijcard.2018.03.093 Seferović PM, Coats AJS, Ponikowski P, Filippatos G, Huelsmann M, Jhund PS et al (2020) European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose-lowering drugs in patients with heart failure. Eur J Heart Fail 22(2):196–213. https://doi.org/10.1002/ejhf.1673 (Epub 2019 Dec 9. PMID: 31816162) Mullens W, Martens P, Forouzan O, Dauw J, Vercammen J, Luwel E et al (2020) Effects of dapagliflozin on congestion assessed by remote pulmonary artery pressure monitoring. ESC Heart Fail 7:2071–2073. https://doi.org/10.1002/ehf2.12850 Nassif ME, Qintar M, Windsor SL, Jermyn R, Shavelle DM, Tang F et al (2021) Empagliflozin effects on pulmonary artery pressure in patients with heart failure: results from the EMBRACE-HF trial. Circulation 143:1673–1686. https://doi.org/10.1161/CIRCULATIONAHA.120.052503 Shavelle DM, Desai AS, Abraham WT, Bourge RC, Raval N, Rathman LD, CardioMEMS Post-Approval Study Investigators et al (2020) Lower rates of heart failure and all-cause hospitalisation during pulmonary artery pressure-guided therapy for ambulatory heart failure. Circ Heart Fail 13:e006863. https://doi.org/10.1161/CIRCHEARTFAILURE.119.006863 Heywood JT, Jermyn R, Shavelle D, Abraham WT, Bhimaraj A, Bhatt K et al (2017) Impact of practice-based management of pulmonary artery pressures in 2000 patients implanted with the CardioMEMS sensor. Circulation 135:1509–1517. https://doi.org/10.1161/CIRCULATIONAHA.116.026184 Vaduganathan M, DeFilippis EM, Fonarow GC, Butler J, Mehra MR (2017) Postmarketing adverse events related to the CardioMEMS HF system. JAMA Cardiol 2:1277–1279. https://doi.org/10.1001/jamacardio.2017.3791 Angermann CE, Assmus B, Anker SD, Asselbergs FW, Brachmann J, Brett ME et al (2020) Pulmonary artery pressure-guided therapy in ambulatory patients with symptomatic heart failure: the CardioMEMS European monitoring study for heart failure. Eur J Heart Fail 22:1891–1901. https://doi.org/10.1002/ejhf.1943 Cowie MR, Flett A, Cowburn P, Foley P, Chandrasekaran B, Loke I et al (2022) Real-world evidence in a national health service: results of the UK CardioMEMS HF System Post-Market Study. ESC Heart Fail 9:48–56. https://doi.org/10.1002/ehf2.13748 Sandhu AT, Goldhaber-Fiebert JD, Owens DK, Turakhia MP, Kaiser DW, Heidenreich PA (2016) Cost effectiveness of implantable pulmonary artery pressure monitoring in chronic heart failure. J Am Coll Cardiol HF 4:368–375. https://doi.org/10.1016/j.jchf.2015.12.015 Cleland JGF, Tavazzi L, Daubert JC, Tageldien A, Freemantle N (2009) Cardiac resynchronization therapy: are modern myths preventing appropriate use? J Am Coll Cardiol 53:608–611. https://doi.org/10.1016/j.jacc.2008.10.040 Mullens W, Sharif F, Dupont M, Rothman AMK, Wijns W (2020) Digital health care solution for proactive heart failure management with the Cordella Heart Failure System: results of the SIRONA first-in-human study. Eur J Heart Fail. 22(10):1912–1919. https://doi.org/10.1002/ejhf.1870 (Epub 2020 May 31, PMID: 32476191; PMCID: PMC7687200) Perl L, Meerkin D, D’amario D, Avraham BB, Gal TB, Weitsman T et al (2022) The V-LAP system for remote left atrial pressure monitoring of patients with heart failure: remote left atrial pressure monitoring. J Card Fail S1071–9164(22):00004–00005. https://doi.org/10.1016/j.cardfail.2021.12.019 Ivey-Miranda JB, Wetterling F, Gaul R, Sheridan S, Asher JL, Rao VS et al (2021) Changes in inferior vena cava represents a more sensitive metric than change in filling pressures during experimental manipulation of intravascular volume and tone. Eur J Heart Fail. https://doi.org/10.1002/ejhf.2395 Pellicori P, Platz E, Dauw J, Ter Maaten JM, Martens P, Pivetta E et al (2021) Ultrasound imaging of congestion in heart failure: examinations beyond the heart. Eur J Heart Fail 23(5):703–712. https://doi.org/10.1002/ejhf.2032