Perioperative Management of Pulmonary Hypertension. A Review

1Rich S, Haworth SG, Hassoun PM, Yacoub MH. Pulmonary hypertension: The unaddressed global health burden. Lancet Respir Med. 2018;6:577–9.Rich S Haworth SG Hassoun PM Yacoub MH Pulmonary hypertension: The unaddressed global health burden Lancet Respir Med 20186577 910.1016/S2213-2600(18)30268-6Search in Google Scholar

2Simonneau G, Montani D, Celermajer DS, Denton CP, Gatzoulis MA, Krowka M, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53:1801913.Simonneau G Montani D Celermajer DS Denton CP Gatzoulis MA Krowka M et al Haemodynamic definitions and updated clinical classification of pulmonary hypertension Eur Respir J 201953180191310.1183/13993003.01913-2018635133630545968Search in Google Scholar

3Frost AE, Badesch DB, Barst RJ, Benza RL, Elliott CG, Farber HW, et al. The Changing Picture of Patients With Pulmonary Arterial Hypertension in the United States. Chest. 2011;139:128–37.Frost AE Badesch DB Barst RJ Benza RL Elliott CG Farber HW et al The Changing Picture of Patients With Pulmonary Arterial Hypertension in the United States Chest 2011139128 3710.1378/chest.10-007520558556Search in Google Scholar

4Ling Y, Johnson MK, Kiely DG, Condliffe R, Elliot CA, Gibbs JSR, et al. Changing Demographics, Epidemiology and Survival of Incident Pulmonary Arterial Hypertension. Am J Respir Crit Care Med. 2012;186:790–6.Ling Y Johnson MK Kiely DG Condliffe R Elliot CA Gibbs JSR et al Changing Demographics, Epidemiology and Survival of Incident Pulmonary Arterial Hypertension Am J Respir Crit Care Med 2012186790 610.1164/rccm.201203-0383OC22798320Search in Google Scholar

5Lau EMT, Giannoulatou E, Celermajer DS, Humbert M. Epidemiology and treatment of pulmonary arterial hypertension. Nat Rev Cardiol. 2017;14:603–14.Lau EMT Giannoulatou E Celermajer DS Humbert M Epidemiology and treatment of pulmonary arterial hypertension Nat Rev Cardiol 201714603 1410.1038/nrcardio.2017.8428593996Search in Google Scholar

6Hiraide T, Kataoka M, Suzuki H, Aimi Y, Chiba T, Isobe S, et al. Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension. J Hear Lung Transplant. 2020;39:103–12.Hiraide T Kataoka M Suzuki H Aimi Y Chiba T Isobe S et al Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension J Hear Lung Transplant 202039103 1210.1016/j.healun.2019.08.02231542298Search in Google Scholar

7Hoeper MM, Galié N, Murali S, Olschewski H, Rubenfire M, Robbins IM, et al. Outcome after cardiopulmonary resuscitation in patients with pulmonary arterial hypertension. Am J Respir Crit Care Med. 2002;165:341–4.Hoeper MM Galié N Murali S Olschewski H Rubenfire M Robbins IM et al Outcome after cardiopulmonary resuscitation in patients with pulmonary arterial hypertension Am J Respir Crit Care Med 2002165341 410.1164/ajrccm.165.3.200109-0130c11818318Search in Google Scholar

8Galiè N, Humbert M, Vachiery J-L, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2015;46:903–75.Galiè N Humbert M Vachiery J-L Gibbs S Lang I Torbicki A et al 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension Eur Respir J 201546903 7510.1183/13993003.01032-201526318161Search in Google Scholar

9Naeije R, Chin K. Differentiating Precapillary From Postcapillary Pulmonary Hypertension. Circulation. 2019;140:712–4.Naeije R Chin K Differentiating Precapillary From Postcapillary Pulmonary Hypertension Circulation 2019140712 410.1161/CIRCULATIONAHA.119.04029531449453Search in Google Scholar

10Lai YC, Potoka KC, Champion HC, Mora AL, Gladwin MT. Pulmonary arterial hypertension: The clinical syndrome. Circ Res. 2014;115:115–30.Lai YC Potoka KC Champion HC Mora AL Gladwin MT Pulmonary arterial hypertension: The clinical syndrome Circ Res 2014115115 3010.1161/CIRCRESAHA.115.301146409668624951762Search in Google Scholar

11Ghigna M-R, Dorfmüller P. Pulmonary vascular disease and pulmonary hypertension. Diagnostic Histopathol. 2019;25:304– 12.Ghigna M-R Dorfmüller P Pulmonary vascular disease and pulmonary hypertension Diagnostic Histopathol 201925:304–1210.1016/j.mpdhp.2019.05.002Search in Google Scholar

12S. A-OM, Stuart S, Boyle AJ, Sverdlov AL, Collins NJ. Pulmonary Hypertension Due to Left Heart Disease. Hypertension. 2020;75:1397–408.A-OM S. Stuart S Boyle AJ Sverdlov AL Collins NJ Pulmonary Hypertension Due to Left Heart Disease Hypertension 2020751397 40810.1161/HYPERTENSIONAHA.119.1433032336230Search in Google Scholar

13Fishman AP, McClement J, Himmelstein A, Cournand A. Effects of acute anoxia on the circulation and respiration in patients with chronic pulmonary disease studied during the steady state. J Clin Invest. 1952;31:770–81.Fishman AP McClement J Himmelstein A Cournand A Effects of acute anoxia on the circulation and respiration in patients with chronic pulmonary disease studied during the steady state J Clin Invest 195231770 8110.1172/JCI10266243647314955529Search in Google Scholar

14Peinado VI, Barberà JA, Abate P, Ramírez J, Roca J, Santos S, et al. Inflammatory reaction in pulmonary muscular arteries of patients with mild chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;159:1605–11.Peinado VI Barberà JA Abate P Ramírez J Roca J Santos S et al Inflammatory reaction in pulmonary muscular arteries of patients with mild chronic obstructive pulmonary disease Am J Respir Crit Care Med 19991591605 1110.1164/ajrccm.159.5.980705910228134Search in Google Scholar

15Moser KM, Bloor CM. Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension. Chest. 1993;1:685–92.Moser KM Bloor CM Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension Chest 19931685 9210.1378/chest.103.3.6858449052Search in Google Scholar

16Crystal GJ, Pagel PS. Right Ventricular Perfusion: Physiology and Clinical Implications. Anesthesiology. 2018;128:202–18.Crystal GJ Pagel PS Right Ventricular Perfusion: Physiology and Clinical Implications Anesthesiology 2018128202 1810.1097/ALN.000000000000189128984631Search in Google Scholar

17Zong P, Tune JD, Downey HF. Mechanisms of oxygen demand/supply balance in the right ventricle. Exp Biol Med. 2005;280:507–19.Zong P Tune JD Downey HF Mechanisms of oxygen demand/supply balance in the right ventricle Exp Biol Med 2005280507 1910.1177/15353702052300080116118400Search in Google Scholar

18Hart BJ, Bian X, Gwirtz PA, Setty S, Downey HF. Right ventricular oxygen supply/demand balance in exercising dogs. Am J Physiol - Hear Circ Physiol. 2001;281:H823-30.Hart BJ Bian X Gwirtz PA Setty S Downey HF Right ventricular oxygen supply/demand balance in exercising dogs Am J Physiol - Hear Circ Physiol 2001281H823 3010.1152/ajpheart.2001.281.2.H82311454587Search in Google Scholar

19Guarracino F, Cariello C, Danella A, Doroni L, Lapolla F, Vullo C, Pasquini C, Stefani M. Right ventricular failure: physiology and assessment. Minerva Anestesiol. 2005;71:307–12.Guarracino F Cariello C Danella A Doroni L Lapolla F Vullo C Pasquini C Stefani M Right ventricular failure: physiology and assessment Minerva Anestesiol 200571307 12Search in Google Scholar

20Yonekura S, Watanabe N, Downey HF. Transmural variation in autoregulation of right ventricular blood flow. Circ Res. 1988;62:776–81.Yonekura S Watanabe N Downey HF Transmural variation in autoregulation of right ventricular blood flow Circ Res 198862776 8110.1161/01.RES.62.4.776Search in Google Scholar

21Rosenkranz S, Gibbs JSR, Wachter R, De Marco T, Vonk-Noordegraaf A, Vachiéry J-L. Left ventricular heart failure and pulmonary hypertension. Eur Heart J. 2016;37:942–54.Rosenkranz S Gibbs JSR Wachter R De Marco T Vonk-Noordegraaf A Vachiéry J-L Left ventricular heart failure and pulmonary hypertension Eur Heart J 201637942 5410.1093/eurheartj/ehv512480017326508169Search in Google Scholar

22Haddad F, Couture P, Tousignant C, Denault AY. The right ventricle in cardiac surgery, a perioperative perspective: I. anatomy, physiology, and assessment. Anesth Analg. 2009;108:422–33.Haddad F Couture P Tousignant C Denault AY The right ventricle in cardiac surgery, a perioperative perspective: I anatomy, physiology, and assessment. Anesth Analg 2009108422 3310.1213/ane.0b013e31818d8b92Search in Google Scholar

23Baumgart D, Haude M, Görge G, Liu F, Ge J, Große-Eggebrecht C, et al. Augmented α-adrenergic constriction of atherosclerotic human coronary arteries. Circulation. 1999;99:2090–7.Baumgart D Haude M Görge G Liu F Ge J Große-Eggebrecht C et al Augmented α-adrenergic constriction of atherosclerotic human coronary arteries Circulation 1999992090 710.1161/01.CIR.99.16.2090Search in Google Scholar

24Murphree SS, Saffitz JE. Delineation of the distribution of β-adrenergic receptor subtypes in canine myocardium. Circ Res. 1988;63:117–25.Murphree SS Saffitz JE Delineation of the distribution of β-adrenergic receptor subtypes in canine myocardium Circ Res 198863117 2510.1161/01.RES.63.1.117Search in Google Scholar

25Crystal GJ, Zhou X, Alam S, Piotrowski A, Hu G. Lack of role for nitric oxide in cholinergic modulation of myocardial contractility in vivo. Am J Physiol - Hear Circ Physiol. 2001;281:H198-206.Crystal GJ Zhou X Alam S Piotrowski A Hu G Lack of role for nitric oxide in cholinergic modulation of myocardial contractility in vivo Am J Physiol - Hear Circ Physiol 2001281H198 20610.1152/ajpheart.2001.281.1.H198Search in Google Scholar

26Runo JR, Loyd JE. Primary pulmonary hypertension. Lancet. 2003;361:1533–44.Runo JR Loyd JE Primary pulmonary hypertension Lancet 20033611533 4410.1016/S0140-6736(03)13167-4Search in Google Scholar

27Le RJ, Fenstad ER, Maradit-Kremers H, McCully RB, Frantz RP, McGoon MD, et al. Syncope in adults with pulmonary arterial hypertension. J Am Coll Cardiol. 2011;58:863–7.Le RJ Fenstad ER Maradit-Kremers H McCully RB Frantz RP McGoon MD et al Syncope in adults with pulmonary arterial hypertension J Am Coll Cardiol 201158863 710.1016/j.jacc.2011.04.02621835323Search in Google Scholar

28Mandras SA, Mehta HS, Vaidya A. Pulmonary Hypertension: A Brief Guide for Clinicians. Mayo Clin Proc. 2020;95:1978–88.Mandras SA Mehta HS Vaidya A Pulmonary Hypertension: A Brief Guide for Clinicians Mayo Clin Proc 2020951978 8810.1016/j.mayocp.2020.04.03932861339Search in Google Scholar

29Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. 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): Endor. Eur Heart J. 2016;37:67–119.Galiè N Humbert M Vachiery JL Gibbs S Lang I Torbicki A et al 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): Endor Eur Heart J 20163767 11910.1093/eurheartj/ehv31726320113Search in Google Scholar

30Altschul E, Remy-Jardin M, Machnicki S, Sulica R, Moore JA, Singh A, et al. Imaging of Pulmonary Hypertension: Pictorial Essay. Chest. 2019;156:211–27.Altschul E Remy-Jardin M Machnicki S Sulica R Moore JA Singh A et al Imaging of Pulmonary Hypertension: Pictorial Essay Chest 2019156211 2710.1016/j.chest.2019.04.00330981724Search in Google Scholar

31Augustine DX, Coates-Bradshaw LD, Willis J, Harkness A, Ring L, Grapsa J, et al. Echocardiographic assessment of pulmonary hypertension: A guideline protocol from the British Society of Echocardiography. Echo Res Pract. 2018;5:11–24.Augustine DX Coates-Bradshaw LD Willis J Harkness A Ring L Grapsa J et al Echocardiographic assessment of pulmonary hypertension: A guideline protocol from the British Society of Echocardiography Echo Res Pract 2018511 2410.1530/ERP-17-0071605550930012832Search in Google Scholar

32Ristow B, Ahmed S, Wang L, Liu H, Angeja BG, Whooley MA, et al. Pulmonary regurgitation end-diastolic gradient is a doppler marker of cardiac status: Data from the heart and soul study. J Am Soc Echocardiogr. 2005;18:885–91.Ristow B Ahmed S Wang L Liu H Angeja BG Whooley MA et al Pulmonary regurgitation end-diastolic gradient is a doppler marker of cardiac status: Data from the heart and soul study J Am Soc Echocardiogr 200518885 9110.1016/j.echo.2005.06.004Search in Google Scholar

33Kyranis S, Latona J, Savage M, Kelly N, Burstow D, Scalia G, et al. Tricuspid Regurgitation Velocity in the Assessment of Pulmonary Hypertension: Is it Accurate at All? Hear Lung Circ. 2016;25:257.Kyranis S Latona J Savage M Kelly N Burstow D Scalia G et al Tricuspid Regurgitation Velocity in the Assessment of Pulmonary Hypertension: Is it Accurate at All? Hear Lung Circ 20162525710.1016/j.hlc.2016.06.597Search in Google Scholar

34Sun XG, Hansen JE, Oudiz RJ, Wasserman K. Pulmonary function in primary pulmonary hypertension. J Am Coll Cardiol. 2003;41:1028–35.Sun XG Hansen JE Oudiz RJ Wasserman K Pulmonary function in primary pulmonary hypertension J Am Coll Cardiol 2003411028 3510.1016/S0735-1097(02)02964-9Search in Google Scholar

35Rich S, Dantzker DR, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med. 1987;107:216–23.Rich S Dantzker DR Ayres SM Bergofsky EH Brundage BH Detre KM et al Primary pulmonary hypertension A national prospective study. Ann Intern Med 1987107216 2310.7326/0003-4819-107-2-216Search in Google Scholar

36Low AT, Medford ARL, Millar AB, Tulloh RMR. Lung function in pulmonary hypertension. Respir Med. 2015;109:1244–9.Low AT Medford ARL Millar AB Tulloh RMR Lung function in pulmonary hypertension Respir Med 20151091244 910.1016/j.rmed.2015.05.022Search in Google Scholar

37Hosenpud JD, Stibolt TA, Atwal K, Shelley D. Abnormal pulmonary function specifically related to congestive heart failure: Comparison of patients before and after cardiac transplantation. Am J Med. 1990;88:493–6.Hosenpud JD Stibolt TA Atwal K Shelley D Abnormal pulmonary function specifically related to congestive heart failure: Comparison of patients before and after cardiac transplantation Am J Med 199088493 610.1016/0002-9343(90)90428-GSearch in Google Scholar

38Steenhuis LH, Groen HJM, Koeter GH, Van der Mark TW. Diffusion capacity and haemodynamics in primary and chronic thromboembolic pulmonary hypertension. Eur Respir J. 2000;16:276–81.Steenhuis LH Groen HJM Koeter GH Van der Mark TW Diffusion capacity and haemodynamics in primary and chronic thromboembolic pulmonary hypertension Eur Respir J 200016276 8110.1034/j.1399-3003.2000.16b15.x10968503Search in Google Scholar

39Levett DZH, Jack S, Swart M, Carlisle J, Wilson J, Snowden C, et al. Perioperative cardiopulmonary exercise testing (CPET): consensus clinical guidelines on indications, organization, conduct, and physiological interpretation. Br J Anaesth. 2018;120:484–500.Levett DZH Jack S Swart M Carlisle J Wilson J Snowden C et al Perioperative cardiopulmonary exercise testing (CPET): consensus clinical guidelines on indications, organization, conduct, and physiological interpretation Br J Anaesth 2018120484 50010.1016/j.bja.2017.10.02029452805Search in Google Scholar

40Farina S, Correale M, Bruno N, Paolillo S, Salvioni E, Badagliacca R, et al. The role of cardiopulmonary exercise tests in pulmonary arterial hypertension. Eur Respir Rev. 2018;27:170134.Farina S Correale M Bruno N Paolillo S Salvioni E Badagliacca R et al The role of cardiopulmonary exercise tests in pulmonary arterial hypertension Eur Respir Rev 20182717013410.1183/16000617.0134-201729720508Search in Google Scholar

41Robertson HT. Dead space: The physiology of wasted ventilation. Eur Respir J. 2015;45:1704–16.Robertson HT Dead space: The physiology of wasted ventilation Eur Respir J 2015451704 1610.1183/09031936.0013761425395032Search in Google Scholar

42Rosenkranz S, Preston IR. Right heart catheterisation: best practice and pitfalls in pulmonary hypertension. Eur Respir Rev. 2015;24:642– 52.Rosenkranz S Preston IR Right heart catheterisation: best practice and pitfalls in pulmonary hypertension Eur Respir Rev 201524642–5210.1183/16000617.0062-2015Search in Google Scholar

43Chatterjee NA, Lewis GD. What is the prognostic significance of pulmonary hypertension in heart failure? Circ Heart Fail. 2011;4:541–5.Chatterjee NA Lewis GD What is the prognostic significance of pulmonary hypertension in heart failure? Circ Heart Fail 20114541 510.1161/CIRCHEARTFAILURE.111.963785Search in Google Scholar

44Shanmugam E, Jena A, George M. Riociguat: Something new in pulmonary hypertension therapeutics? J Pharmacol Pharmacother. 2015;6:3–6.Shanmugam E Jena A George M Riociguat: Something new in pulmonary hypertension therapeutics? J Pharmacol Pharmacother 201563 610.4103/0976-500X.149132Search in Google Scholar

45Desai A, Desouza SA. Treatment of pulmonary hypertension with left heart disease: A concise review. Vasc Health Risk Manag. 2017;13:415–20.Desai A Desouza SA Treatment of pulmonary hypertension with left heart disease: A concise review Vasc Health Risk Manag 201713415 2010.2147/VHRM.S111597Search in Google Scholar

46Kim NH, Delcroix M, Jais X, Madani MM, Matsubara H, Mayer E, et al. Chronic thromboembolic pulmonary hypertension. Eur Respir J. 2019;53:1801915Kim NH Delcroix M Jais X Madani MM Matsubara H Mayer E et al Chronic thromboembolic pulmonary hypertension Eur Respir J 201953180191510.1183/13993003.01915-2018Search in Google Scholar

47Lang I, Meyer BC, Ogo T, Matsubara H, Kurzyna M, Ghofrani HA, et al. Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension. Eur Respir Rev. 2017;26:160119.Lang I Meyer BC Ogo T Matsubara H Kurzyna M Ghofrani HA et al Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension Eur Respir Rev 20172616011910.1183/16000617.0119-2016Search in Google Scholar

48Simonneau G, D’Armini AM, Ghofrani HA, Grimminger F, Jansa P, Kim NH, et al. Predictors of long-term outcomes in patients treated with riociguat for chronic thromboembolic pulmonary hypertension: Data from the CHEST-2 open-label, randomised, long-term extension trial. Lancet Respir Med. 2016;4:372–80.Simonneau G D’Armini AM Ghofrani HA Grimminger F Jansa P Kim NH et al Predictors of long-term outcomes in patients treated with riociguat for chronic thromboembolic pulmonary hypertension: Data from the CHEST-2 open-label, randomised, long-term extension trial Lancet Respir Med 20164372 8010.1016/S2213-2600(16)30022-4Search in Google Scholar

49Ghofrani HA, Simonneau G, D’Armini AM, Fedullo P, Howard LS, Jaïs X, et al. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study. Lancet Respir Med. 2017;5:785–94.Ghofrani HA Simonneau G D’Armini AM Fedullo P Howard LS Jaïs X et al Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study Lancet Respir Med 20175785 9410.1016/S2213-2600(17)30305-3Search in Google Scholar

50Jaïs X, D’Armini AM, Jansa P, Torbicki A, Delcroix M, Ghofrani HA, et al. Bosentan for Treatment of Inoperable Chronic Thromboembolic Pulmonary Hypertension. BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a Randomized, Placebo-Controlled Trial. J Am Coll Cardiol. 2008;52:2127–34.Jaïs X D’Armini AM Jansa P Torbicki A Delcroix M Ghofrani HA et al Bosentan for Treatment of Inoperable Chronic Thromboembolic Pulmonary Hypertension BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a Randomized, Placebo-Controlled Trial. J Am Coll Cardiol 2008522127 3410.1016/j.jacc.2008.08.05919095129Search in Google Scholar

51Francis SH, Busch JL, Corbin JD. cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev. 2010;62:525–63.Francis SH Busch JL Corbin JD cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action Pharmacol Rev 201062525 6310.1124/pr.110.002907296490220716671Search in Google Scholar

52Said K. Riociguat: PATENT-1 Study. Glob Cardiol Sci Pract. 2014;2014:31–5.Said K Riociguat: PATENT-1 Study Glob Cardiol Sci Pract 2014201431 510.5339/gcsp.2014.21422043025405174Search in Google Scholar

53Galiè N, Olschewski H, Oudiz RJ, Torres F, Frost A, Ghofrani HA, et al. Ambrisentan for the treatment of pulmonary arterial hypertension: Results of the ambrisentan in pulmonary arterial hypertension, randomized, double-Blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation. 2008;117:3010–19.Galiè N Olschewski H Oudiz RJ Torres F Frost A Ghofrani HA et al Ambrisentan for the treatment of pulmonary arterial hypertension: Results of the ambrisentan in pulmonary arterial hypertension, randomized, double-Blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2 Circulation 20081173010 1910.1161/CIRCULATIONAHA.107.74251018506008Search in Google Scholar

54Miyauchi T, Sakai S. Endothelin and the heart in health and diseases. Peptides. 2019;111:77–88.Miyauchi T Sakai S Endothelin and the heart in health and diseases Peptides 201911177 8810.1016/j.peptides.2018.10.00230352269Search in Google Scholar

55Wei A, Gu Z, Li J, Liu X, Wu X, Han Y, et al. Clinical Adverse Effects of Endothelin Receptor Antagonists: Insights From the Meta-Analysis of 4894 Patients From 24 Randomized Double-Blind Placebo-Controlled Clinical Trials. J Am Heart Assoc. 2016;5:e003896.Wei A Gu Z Li J Liu X Wu X Han Y et al Clinical Adverse Effects of Endothelin Receptor Antagonists: Insights From the Meta-Analysis of 4894 Patients From 24 Randomized Double-Blind Placebo-Controlled Clinical Trials J Am Heart Assoc 20165e00389610.1161/JAHA.116.003896521031927912207Search in Google Scholar

56Mitchell JA, Ahmetaj-Shala B, Kirkby NS, Wright WR, Mackenzie LS, Reed DM, et al. Role of prostacyclin in pulmonary hypertension. Glob Cardiol Sci Pract. 2014;4:382–93.Mitchell JA Ahmetaj-Shala B Kirkby NS Wright WR Mackenzie LS Reed DM et al Role of prostacyclin in pulmonary hypertension Glob Cardiol Sci Pract 20144382 9310.5339/gcsp.2014.53435551325780793Search in Google Scholar

57Hoeper MM, Kramer T, Pan Z, Eichstaedt CA, Spiesshoefer J, Benjamin N, et al. Mortality in pulmonary arterial hypertension: Prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J. 2017;50:1700740.Hoeper MM Kramer T Pan Z Eichstaedt CA Spiesshoefer J Benjamin N et al Mortality in pulmonary arterial hypertension: Prediction by the 2015 European pulmonary hypertension guidelines risk stratification model Eur Respir J 201750170074010.1183/13993003.00740-201728775047Search in Google Scholar

58Benza RL, Elliott CG, Farber HW, Foreman AJ, Frost AE, Gomberg-Maitland M, et al. Updated Risk Score Calculator for Patients with Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL). Am J Respir Crit Care Med. 2017;195:A6899.Benza RL Elliott CG Farber HW Foreman AJ Frost AE Gomberg-Maitland M et al Updated Risk Score Calculator for Patients with Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Am J Respir Crit Care Med 2017195A6899Search in Google Scholar

59Robitaille A, Denault AY, Couture P, Bélisle S, Fortier A, Guertin MC, et al. Importance of Relative Pulmonary Hypertension in Cardiac Surgery: The Mean Systemic-to-Pulmonary Artery Pressure Ratio. J Cardiothorac Vasc Anesth. 2006;20:331–9.Robitaille A Denault AY Couture P Bélisle S Fortier A Guertin MC et al Importance of Relative Pulmonary Hypertension in Cardiac Surgery: The Mean Systemic-to-Pulmonary Artery Pressure Ratio J Cardiothorac Vasc Anesth 200620331 910.1053/j.jvca.2005.11.01816750732Search in Google Scholar

60Bapat V, Rajagopal V, Meduri C, Farivar RS, Walton A, Duffy SJ, et al. Early Experience With New Transcatheter Mitral Valve Replacement. J Am Coll Cardiol. 2018;13:344–51.Bapat V Rajagopal V Meduri C Farivar RS Walton A Duffy SJ et al Early Experience With New Transcatheter Mitral Valve Replacement J Am Coll Cardiol 201813344 5110.1016/j.jacc.2017.10.06129102689Search in Google Scholar

61Kaw R, Pasupuleti V, Deshpande A, Hamieh T, Walker E, Minai OA. Pulmonary hypertension: An important predictor of outcomes in patients undergoing non-cardiac surgery. Respir Med. 2011;105:619–24.Kaw R Pasupuleti V Deshpande A Hamieh T Walker E Minai OA Pulmonary hypertension: An important predictor of outcomes in patients undergoing non-cardiac surgery Respir Med 2011105619 2410.1016/j.rmed.2010.12.00621195595Search in Google Scholar

62Lai HC, Lai HC, Wang KY, Lee WL, Ting CT, Liu TJ. Severe pulmonary hypertension complicates postoperative outcome of non-cardiac surgery. Br J Anaesth. 2007;99:184–90.Lai HC Lai HC Wang KY Lee WL Ting CT Liu TJ Severe pulmonary hypertension complicates postoperative outcome of non-cardiac surgery Br J Anaesth 200799184 9010.1093/bja/aem12617576968Search in Google Scholar

63Ramakrishna G, Sprung J, Ravi BS, Chandrasekaran K, McGoon MD. Impact of pulmonary hypertension on the outcomes of noncardiac surgery: Predictors of perioperative morbidity and mortality. J Am Coll Cardiol. 2005;45:1691–9.Ramakrishna G Sprung J Ravi BS Chandrasekaran K McGoon MD Impact of pulmonary hypertension on the outcomes of noncardiac surgery: Predictors of perioperative morbidity and mortality J Am Coll Cardiol 2005451691 910.1016/j.accreview.2005.08.229Search in Google Scholar

64Montani D, Bergot E, Günther S, Savale L, Bergeron A, Bourdin A, et al. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation. 2012;70:239–43.Montani D Bergot E Günther S Savale L Bergeron A Bourdin A et al Pulmonary arterial hypertension in patients treated by dasatinib Circulation 201270239 4310.1161/CIRCULATIONAHA.111.07992122451584Search in Google Scholar

65Fuster V, Steele PM, Edwards WD, Gersh BJ, McGoon MD, Frye RL. Primary pulmonary hypertension: Natural history and the importance of thrombosis. Circulation. 1984;70:580–7.Fuster V Steele PM Edwards WD Gersh BJ McGoon MD Frye RL Primary pulmonary hypertension: Natural history and the importance of thrombosis Circulation 198470580 710.1161/01.CIR.70.4.580Search in Google Scholar

66Huber K, Beckmann R, Frank H, Kneussl M, Mlczoch J, Binder BR. Fibrinogen, t-PA, and PAI-1 plasma levels in patients with pulmonary hypertension. Am J Respir Crit Care Med. 1994;150:929–33.Huber K Beckmann R Frank H Kneussl M Mlczoch J Binder BR Fibrinogen, t-PA, and PAI-1 plasma levels in patients with pulmonary hypertension Am J Respir Crit Care Med 1994150929 3310.1164/ajrccm.150.4.79214657921465Search in Google Scholar

67Rich S, Kaufmann E, Levy PS. The Effect of High Doses of Calcium-Channel Blockers on Survival in Primary Pulmonary Hypertension. N Engl J Med. 1992;327:76–81.Rich S Kaufmann E Levy PS The Effect of High Doses of Calcium-Channel Blockers on Survival in Primary Pulmonary Hypertension N Engl J Med 199232776 8110.1056/NEJM1992070932702031603139Search in Google Scholar

68Sarkar MS, Desai PM. Pulmonary hypertension and cardiac anesthesia: Anesthesiologist’s perspective. Ann Card Anaesth. 2018;21:116–22.Sarkar MS Desai PM Pulmonary hypertension and cardiac anesthesia: Anesthesiologist’s perspective Ann Card Anaesth 201821116 22Search in Google Scholar

69Teo YW, Greenhalgh DL. Update on anaesthetic approach to pulmonary hypertension. Eur J Anaesthesiol. 2010;24:317–23.Teo YW Greenhalgh DL Update on anaesthetic approach to pulmonary hypertension Eur J Anaesthesiol 201024317 2310.1097/EJA.0b013e328335474e20010107Search in Google Scholar

70Yilmaz S, Yildirim Y, Taylan M, Demir M, Yilmaz Z, Kara AV, et al. The relationship of fluid overload as assessed by bioelectrical impedance analysis with pulmonary arterial hypertension in hemodialysis patients. Med Sci Monit. 2016;22:488–494.Yilmaz S Yildirim Y Taylan M Demir M Yilmaz Z Kara AV et al The relationship of fluid overload as assessed by bioelectrical impedance analysis with pulmonary arterial hypertension in hemodialysis patients Med Sci Monit 201622488 49410.12659/MSM.896305Search in Google Scholar

71Stickel S, Gin-Sing W, Wagenaar M, Gibbs JSR. The practical management of fluid retention in adults with right heart failure due to pulmonary arterial hypertension. Eur Heart J Suppl. 2019;21:46–53.Stickel S Gin-Sing W Wagenaar M Gibbs JSR The practical management of fluid retention in adults with right heart failure due to pulmonary arterial hypertension Eur Heart J Suppl 20192146 5310.1093/eurheartj/suz207691505531857800Search in Google Scholar

72Pilkington SA, Taboada D, Martinez G. Pulmonary hypertension and its management in patients undergoing non-cardiac surgery. Anaesthesia. 2015;7:56–70.Pilkington SA Taboada D Martinez G Pulmonary hypertension and its management in patients undergoing non-cardiac surgery Anaesthesia 2015756 7010.1111/anae.1283125267493Search in Google Scholar

73Nonaka DF, Grichnik KP, Whitener GB. Pulmonary Hypertension and Thoracic Surgery: Diagnostics and Advances in Therapy and Intraoperative Management. Curr Anesthesiol Rep. 2014;4:135–41.Nonaka DF Grichnik KP Whitener GB Pulmonary Hypertension and Thoracic Surgery: Diagnostics and Advances in Therapy and Intraoperative Management Curr Anesthesiol Rep 20144135 4110.1007/s40140-014-0053-xSearch in Google Scholar

74J Jenkins, A Lynn, J Edmonds GB. Effects of Mechanical Ventilation on Cardiopulmonary Function in Children After Open-Heart Surgery. Crit Care Med. 1985;13:77–80.Jenkins J Lynn A J Edmonds GB Effects of Mechanical Ventilation on Cardiopulmonary Function in Children After Open-Heart Surgery Crit Care Med 19851377 8010.1097/00003246-198502000-000043881223Search in Google Scholar

75Bonnin M, Mercier FJ, Sitbon O, Roger-Christoph S, Jaïs X, Humbert M, et al. Severe pulmonary hypertension during pregnancy: Mode of delivery and anesthetic management of 15 consecutive cases. Anesthesiology. 2005;102:1133–7.Bonnin M Mercier FJ Sitbon O Roger-Christoph S Jaïs X Humbert M et al Severe pulmonary hypertension during pregnancy: Mode of delivery and anesthetic management of 15 consecutive cases Anesthesiology 20051021133 710.1097/00000542-200506000-0001215915025Search in Google Scholar

76Bédard E, Dimopoulos K, Gatzoulis MA. Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension? Eur Heart J. 2009;30:256– 65.Bédard E Dimopoulos K Gatzoulis MA Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension? Eur Heart J 200930256–6510.1093/eurheartj/ehn59719147605Search in Google Scholar

77Martin JT, Tautz TJ, Antognini JF. Safety of regional anesthesia in Eisenmenger’s syndrome. Reg Anesth Pain Med. 2002;27:509– 13.Martin JT Tautz TJ Antognini JF Safety of regional anesthesia in Eisenmenger’s syndrome Reg Anesth Pain Med 200227509–1310.1053/rapm.2002.3570612373701Search in Google Scholar

78Warltier M.D., Ph.D., Editor DC, Campagna M.D., Ph.D. JA, Carter M.D. C. Clinical Relevance of the Bezold–Jarisch Reflex. Anesthesiol J Am Soc Anesthesiol. 2003 May 1;98:1250–60.Warltier MD. Ph.D., Editor DC, Campagna M.D., Ph.D. JA, Carter M.D. C Clinical Relevance of the Bezold–Jarisch Reflex Anesthesiol J Am Soc Anesthesiol 2003 May 1981250 6010.1097/00000542-200305000-0003012717149Search in Google Scholar

79Picard J, Meek T. Complications of regional anaesthesia. Anaesthesia. 2010;65:105–15.Picard J Meek T Complications of regional anaesthesia Anaesthesia 201065105 1510.1111/j.1365-2044.2009.06205.x20377552Search in Google Scholar

80Elgebaly A, Eldabaa A. Is I-gel airway a better option to endotracheal tube airway for sevoflurane-fentanyl anesthesia during cardiac surgery? Anesth Essays Res. 2014;8:216–22.Elgebaly A Eldabaa A Is I-gel airway a better option to endotracheal tube airway for sevoflurane-fentanyl anesthesia during cardiac surgery? Anesth Essays Res 20148216 2210.4103/0259-1162.134510417361525886229Search in Google Scholar

81Grübler Martin R, Olivier W, David B, Stefan B. Basic concepts of heart-lung interactions during mechanical ventilation. Swiss Med Wkly. 2017;147:14491.Grübler Martin R Olivier W David B Stefan B Basic concepts of heart-lung interactions during mechanical ventilation Swiss Med Wkly 20171471449110.4414/smw.2017.1449128944931Search in Google Scholar

82Kerbaul F, Rondelet B, Mote S, Fesler P, Hubloue I, Ewalenko P, et al. Isoflurane and desflurane impair right ventricular-pulmonary arterial coupling in dogs. Anesthesiology. 2004;101:1357–62.Kerbaul F Rondelet B Mote S Fesler P Hubloue I Ewalenko P et al Isoflurane and desflurane impair right ventricular-pulmonary arterial coupling in dogs Anesthesiology 20041011357 6210.1097/00000542-200412000-0001615564943Search in Google Scholar

83Wenker O. Review Of Currently Used Inhalation Anesthetics: Part II. Internet J Anesthesiol. 1998;3:1–11.Wenker O Review Of Currently Used Inhalation Anesthetics: Part II Internet J Anesthesiol 199831 11Search in Google Scholar

84Behnaz F, Ghasemi M, Mohseni G, Zarakim A. The efect of Sevoflurane and Propofol on pulmonary arterial pressure during cardiac catheterization in children with congenital heart diseases. World Fam Med J Fam Med Middle East J Fam Med. 1999;15:54–60.Behnaz F Ghasemi M Mohseni G Zarakim A The efect of Sevoflurane and Propofol on pulmonary arterial pressure during cardiac catheterization in children with congenital heart diseases World Fam Med J Fam Med Middle East J Fam Med 19991554 60Search in Google Scholar

85Naguib M, Samarkandi AH, Bakhamees HS, Magboul MA, El-Bakry AK. Histamine-release haemodynamic changes produced by rocuronium, vecuronium, mivacurium, atracurium and tubocurarine. Br J Anaesth. 1995;75:588–592.Naguib M Samarkandi AH Bakhamees HS Magboul MA El-Bakry AK Histamine-release haemodynamic changes produced by rocuronium, vecuronium, mivacurium, atracurium and tubocurarine Br J Anaesth 199575588 59210.1093/bja/75.5.5887577286Search in Google Scholar

86Recommendations for standards of monitoring during anaesthesia and recovery 2015 . 2015;1:1-9Recommendations for standards of monitoring during anaesthesia and recovery 2015 201511 9Search in Google Scholar

87Cheng JW, Tonelli AR, Petersson G, Krasuski RA. Pharmacologic management of perioperative pulmonary hypertension. J Cardiovasc Pharmacol . 2014;63:375–84.Cheng JW Tonelli AR Petersson G Krasuski RA Pharmacologic management of perioperative pulmonary hypertension J Cardiovasc Pharmacol 201463375 8410.1097/FJC.0000000000000050398220124710471Search in Google Scholar

88Hoeper MM, Granton J. Intensive care unit management of patients with severe pulmonary hypertension and right heart failure. Am J Respir Crit Care Med. 2011;184:1114–24.Hoeper MM Granton J Intensive care unit management of patients with severe pulmonary hypertension and right heart failure Am J Respir Crit Care Med 20111841114 2410.1164/rccm.201104-0662CI21700906Search in Google Scholar

89Lobato EB, Beaver T, Muehlschlegel J, Kirby DS, Klodell C, Sidi A. Treatment with phosphodiesterase inhibitors type III and V: Milrinone and sildenafil is an efective combination during thromboxane-induced acute pulmonary hypertension. Br J Anaesth. 2006;96:317–22.Lobato EB Beaver T Muehlschlegel J Kirby DS Klodell C Sidi A Treatment with phosphodiesterase inhibitors type III and V: Milrinone and sildenafil is an efective combination during thromboxane-induced acute pulmonary hypertension Br J Anaesth 200696317 2210.1093/bja/ael00916443640Search in Google Scholar

90Nieminen MS, Fruhwald S, Heunks LMA, Suominen PK, Gordon AC, Kivikko M, et al. Levosimendan: current data, clinical use and future development. Hear lung Vessel. 2013;5:227–245.Nieminen MS Fruhwald S Heunks LMA Suominen PK Gordon AC Kivikko M et al Levosimendan: current data, clinical use and future development Hear lung Vessel 20135227 245Search in Google Scholar

91Rabanal JM, Real MI, Williams M. Perioperative management of pulmonary hypertension during lung transplantation (a lesson for other anaesthesia setings). Rev Esp Anestesiol Reanim. 2014;61:434–45.Rabanal JM Real MI Williams M Perioperative management of pulmonary hypertension during lung transplantation (a lesson for other anaesthesia setings) Rev Esp Anestesiol Reanim 201461434 4510.1016/j.redar.2014.05.01525156939Search in Google Scholar

92Brunner N, de Jesus Perez VA, Richter A, Haddad F, Denault A, Rojas V, et al. Perioperative pharmacological management of pulmonary hypertensive crisis during congenital heart surgery. Pulm Circ. 2014;4:10–24.Brunner N de Jesus Perez VA Richter A Haddad F Denault A Rojas V et al Perioperative pharmacological management of pulmonary hypertensive crisis during congenital heart surgery Pulm Circ 2014410 2410.1086/674885407076025006417Search in Google Scholar

93Sztrymf B, Souza R, Bertoleti L, Jaïs X, Sitbon O, Price LC, et al. Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension. Eur Respir J. 2010;35:1286– 1293.Sztrymf B Souza R Bertoleti L Jaïs X Sitbon O Price LC et al Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension Eur Respir J 2010351286–129310.1183/09031936.0007020919897557Search in Google Scholar

94Provencher S, Herve P, Jais X, Lebrec D, Humbert M, Simonneau G, et al. Deleterious efects of β-blockers on exercise capacity and hemodynamics in patients with portopulmonary hypertension. Gastroenterology. 2006;130:120–6.Provencher S Herve P Jais X Lebrec D Humbert M Simonneau G et al Deleterious efects of β-blockers on exercise capacity and hemodynamics in patients with portopulmonary hypertension Gastroenterology 2006130120 610.1053/j.gastro.2005.10.01316401475Search in Google Scholar

95Szollosi I, Thompson BR, Krum H, Kaye DM, Naughton MT. Impaired pulmonary difusing capacity and hypoxia in heart failure correlates with central sleep apnea severity. Chest. 2008;134:67–72.Szollosi I Thompson BR Krum H Kaye DM Naughton MT Impaired pulmonary difusing capacity and hypoxia in heart failure correlates with central sleep apnea severity Chest 200813467 7210.1378/chest.07-148718198261Search in Google Scholar

96Savale L, Weatherald J, Jaïs X, Vuillard C, Boucly A, Jevnikar M, et al. Acute decompensated pulmonary hypertension. Eur Respir Rev. 2017;26:170050.Savale L Weatherald J Jaïs X Vuillard C Boucly A Jevnikar M et al Acute decompensated pulmonary hypertension Eur Respir Rev 20172617005010.1183/16000617.0092-201729141964Search in Google Scholar

97Sharman A, Low J. Vasopressin and its role in critical care. Contin Educ Anaesthesia, Crit Care Pain. 2008;8:134–7.Sharman A Low J Vasopressin and its role in critical care Contin Educ Anaesthesia, Crit Care Pain 20088134 710.1093/bjaceaccp/mkn021Search in Google Scholar

98Kreider ME, Hansen-Flaschen J, Ahmad NN, Rossman MD, Kaiser LR, Kucharczuk JC, et al. Complications of Video-Assisted Thoracoscopic Lung Biopsy in Patients with Interstitial Lung Disease. Ann Thorac Surg. 2007;83:1140–4.Kreider ME Hansen-Flaschen J Ahmad NN Rossman MD Kaiser LR Kucharczuk JC et al Complications of Video-Assisted Thoracoscopic Lung Biopsy in Patients with Interstitial Lung Disease Ann Thorac Surg 2007831140 410.1016/j.athoracsur.2006.10.00217307476Search in Google Scholar

99Sullivan B, Puskas F, Fernandez-Bustamante A. Transesophageal Echocardiography in Noncardiac Thoracic Surgery. Anesthesiol Clin. 2012;30:657–69.Sullivan B Puskas F Fernandez-Bustamante A Transesophageal Echocardiography in Noncardiac Thoracic Surgery Anesthesiol Clin 201230657 6910.1016/B978-0-323-71301-6.00055-XSearch in Google Scholar

100Zhang C, Liu Y, Qing E, Ma J. Preoperative risk factors analysis of pulmonary hypertension crisis during perioperative period for caesarean section of woman with severe pulmonary hypertension. Chinese Critical Care Medicine. 2017;29:431– 5.Zhang C Liu Y Qing E Ma J Preoperative risk factors analysis of pulmonary hypertension crisis during perioperative period for caesarean section of woman with severe pulmonary hypertension Chinese Critical Care Medicine 201729431–5Search in Google Scholar

101Olsson KM, Nickel NP, Tongers J, Hoeper MM. Atrial fluter and fibrillation in patients with pulmonary hypertension. Int J Cardiol. 2013;167:2300–5.Olsson KM Nickel NP Tongers J Hoeper MM Atrial fluter and fibrillation in patients with pulmonary hypertension Int J Cardiol 20131672300 510.1016/j.ijcard.2012.06.02422727973Search in Google Scholar

102Peacock A, Ross K. Pulmonary hypertension: A contraindication to the use of β-adrenoceptor blocking agents. Thorax. 2010;65:454–5.Peacock A Ross K Pulmonary hypertension: A contraindication to the use of β-adrenoceptor blocking agents Thorax 201065454 510.1136/thx.2008.11195520435871Search in Google Scholar

103Naeije R, Badagliacca R. The overloaded right heart and ventricular interdependence. Cardiovasc Res. 2017;113:1474– 85.Naeije R Badagliacca R The overloaded right heart and ventricular interdependence Cardiovasc Res 20171131474–8510.1093/cvr/cvx16028957537Search in Google Scholar

104Krowka MJ, Plevak DJ, Findlay JY, Rosen CB, Wiesner RH, Krom RAF. Pulmonary hemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertension undergoing liver transplantation. Liver Transplant. 2000;6:443–50.Krowka MJ Plevak DJ Findlay JY Rosen CB Wiesner RH Krom RAF Pulmonary hemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertension undergoing liver transplantation Liver Transplant 20006443 5010.1053/jlts.2000.635610915166Search in Google Scholar

105Starkel P, Vera A, Gunson B, Mutimer D. Outcome of liver transplantation for patients with pulmonary hypertension. Liver Transplant. 2002;8:382–8.Starkel P Vera A Gunson B Mutimer D Outcome of liver transplantation for patients with pulmonary hypertension Liver Transplant 20028382 810.1053/jlts.2002.3134311965583Search in Google Scholar

106Kruthiventi SC, Kane GC, Sprung J, Weingarten TN, Warner ME. Postoperative pulmonary complications in contemporary cohort of patients with pulmonary hypertension. Bosn J basic Med Sci. 2019;19:392–9.Kruthiventi SC Kane GC Sprung J Weingarten TN Warner ME Postoperative pulmonary complications in contemporary cohort of patients with pulmonary hypertension Bosn J basic Med Sci 201919392 910.17305/bjbms.2019.4332686848831301223Search in Google Scholar

107Ishikawa S , Ohtaki A, Takahashi T, Ohki S, Hasegawa Y, Yamagishi T el al. Lung Impairment Following Cardiac Surgery in Patients With Pulmonary Hypertension. J Cardiovasc Surg. 2002;43:7–10.Ishikawa S Ohtaki A Takahashi T Ohki S Hasegawa Y Yamagishi T el al Lung Impairment Following Cardiac Surgery in Patients With Pulmonary Hypertension J Cardiovasc Surg 2002437 10Search in Google Scholar