Assessment of right ventricular function in the research setting: Knowledge gaps and pathways forward an official American thoracic society research statement

American Journal of Respiratory and Critical Care Medicine

Volumn 198, Issue 4, 2018, Pages e15-e43

  Lahm, Tim ^a   Douglas, Ivor S ^a   Archer, Stephen L ^a   Bogaard, Harm J ^a   Chesler, Naomi C ^a   Haddad, Francois ^a   Hemnes, Anna R ^a   Kawut, Steven M ^a   Kline, Jeffrey A ^a   Kolb, Todd M ^a   Mathai, Stephen C ^a   Mercier, Olaf ^a   Michelakis, Evangelos D ^a   Naeije, Robert ^a   Tuder, Rubin M ^a   Ventetuolo, Corey E ^a   Vieillard Baron, Antoine ^a   Voelkel, Norbert F ^a   Vonk Noordegraaf, Anton ^a   Hassoun, Paul M ^a  

^a NONE

Author keywords

Acute respiratory distress syndrome; Pulmonary circulation; Pulmonary embolism; Pulmonary hypertension; Right ventricle

Indexed keywords

ACUTE DISEASE; CHRONIC DISEASE; EVIDENCE BASED MEDICINE; EXERCISE; HEART RIGHT VENTRICLE FAILURE; HEART RIGHT VENTRICLE FUNCTION; HEART RIGHT VENTRICLE PRESSURE; HEART RIGHT VENTRICLE VOLUME; HEMODYNAMIC PARAMETERS; HUMAN; NONHUMAN; PRIORITY JOURNAL; PULMONARY HYPERTENSION; REVIEW; ANIMAL; DIAGNOSIS; MEDICAL SOCIETY; PATHOPHYSIOLOGY; PHYSIOLOGY; RESEARCH; UNITED STATES;

ANIMALS; HUMANS; RESEARCH; SOCIETIES, MEDICAL; UNITED STATES; VENTRICULAR DYSFUNCTION, RIGHT; VENTRICULAR FUNCTION, RIGHT;

EID: 85051522930     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201806-1160ST     Document Type: Review

References (302)

1. Voelkel NF, Quaife RA, Leinwand LA, Barst RJ, McGoon MD, Meldrum DR, et al.; National Heart, Lung, and Blood Institute Working Group on Cellular and Molecular Mechanisms of Right Heart Failure. Right ventricular function and failure: Report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation 2006;114:1883-1891.
2. Vonk-Noordegraaf A, Haddad F, Chin KM, Forfia PR, Kawut SM, Lumens J, et al. Right heart adaptation to pulmonary arterial hypertension: Physiology and pathobiology. J Am Coll Cardiol 2013; 62:D22-D33.
3. van de Veerdonk MC, Kind T, Marcus JT, Mauritz GJ, Heymans MW, Bogaard HJ, et al. Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy. J Am Coll Cardiol 2011;58:2511-2519.
4. Meyer P, Filippatos GS, Ahmed MI, Iskandrian AE, Bittner V, Perry GJ, et al. Effects of right ventricular ejection fraction on outcomes in chronic systolic heart failure. Circulation 2010;121:252-258.
5. Riedel M, Stanek V, Widimsky J, Prerovsky I. Longterm follow-up of patients with pulmonary thromboembolism: Late prognosis and evolution of hemodynamic and respiratory data. Chest 1982;81: 151-158.
6. Mohammed SF, Hussain I, AbouEzzeddine OF, Takahama H, Kwon SH, Forfia P, et al. Right ventricular function in heart failure with preserved ejection fraction: A community-based study. Circulation 2014;130: 2310-2320.
7. Morrison DA, Adcock K, Collins CM, Goldman S, Caldwell JH, Schwarz MI. Right ventricular dysfunction and the exercise limitation of chronic obstructive pulmonary disease. J Am Coll Cardiol 1987;9:1219-1229.
8. Hyduk A, Croft JB, Ayala C, Zheng K, Zheng ZJ, Mensah GA. Pulmonary hypertension surveillance-United States, 1980-2002. MMWR Surveill Summ 2005;54:1-28.
9. Lloyd-Jones D, Adams RJ, Brown TM, CarnethonM, Dai S, De Simone G, et al.; WRITING GROUP MEMBERS; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2010 update: A report from the American Heart Association. Circulation 2010;121:e46-e215.
10. Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: Appreciating the scope of the heart failure epidemic. JAMA 2003;289:194-202.
11. Erzurum S, Rounds SI, Stevens T, Aldred M, Aliotta J, Archer SL, et al. Strategic plan for lung vascular research: An NHLBI-ORDR workshop report. Am J Respir Crit Care Med 2010;182:1554-1562.
12. Dweik RA, Rounds S, Erzurum SC, Archer S, Fagan K, Hassoun PM, et al.; ATS Committee on Pulmonary Hypertension Phenotypes. An official American Thoracic Society Statement: Pulmonary hypertension phenotypes. Am J Respir Crit Care Med 2014;189:345-355.
13. Haddad F, Doyle R, Murphy DJ, Hunt SA. Right ventricular function in cardiovascular disease, part II: Pathophysiology, clinical importance, and management of right ventricular failure. Circulation 2008;117: 1717-1731.
14. Haddad F, Hunt SA, Rosenthal DN, Murphy DJ. Right ventricular function in cardiovascular disease, part I: Anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation 2008;117:1436-1448.
15. Sandstede J, Lipke C, Beer M, Hofmann S, Pabst T, Kenn W, et al. Ageand gender-specific differences in left and right ventricular cardiac function and mass determined by cine magnetic resonance imaging. Eur Radiol 2000;10:438-442.
16. Grothues F, Moon JC, Bellenger NG, Smith GS, Klein HU, Pennell DJ. Interstudy reproducibility of right ventricular volumes, function, and mass with cardiovascular magnetic resonance. Am Heart J 2004; 147:218-223.
17. Beygui F, Furber A, Delépine S, Helft G, Metzger J-P, Geslin P, et al. Routine breath-hold gradient echo MRI-derived right ventricular mass, volumes and function: Accuracy, reproducibility and coherence study. Int J Cardiovasc Imaging 2004;20:509-516.
18. Kawut SM, Barr RG, Lima JAC, Praestgaard A, Johnson WC, Chahal H, et al. Right ventricular structure is associated with the risk of heart failure and cardiovascular death: The Multi-Ethnic Study of Atherosclerosis (MESA)-right ventricle study. Circulation 2012;126: 1681-1688.
19. Jacobs W, van de Veerdonk MC, Trip P, de Man F, Heymans MW, Marcus JT, et al. The right ventricle explains sex differences in survival in idiopathic pulmonary arterial hypertension. Chest 2014; 145:1230-1236.
20. van Wolferen SA, van de Veerdonk MC, Mauritz G-J, Jacobs W, Marcus JT, Marques KMJ, et al. Clinically significant change in stroke volume in pulmonary hypertension. Chest 2011;139:1003-1009.
21. van Wolferen SA, Marcus JT, Boonstra A, Marques KM, Bronzwaer JG, Spreeuwenberg MD, et al. Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension. Eur Heart J 2007;28:1250-1257.
22. Peacock AJ, Crawley S, McLure L, Blyth K, Vizza CD, Poscia R, et al. Changes in right ventricular function measured by cardiac magnetic resonance imaging in patients receiving pulmonary arterial hypertension-targeted therapy: The EURO-MR study. Circ Cardiovasc Imaging 2014;7:107-114.
23. Forfia PR, Fisher MR, Mathai SC, Housten-Harris T, Hemnes AR, Borlaug BA, et al. Tricuspid annular displacement predicts survival in pulmonary hypertension. Am J Respir Crit Care Med 2006;174: 1034-1041.
24. Sachdev A, Villarraga HR, Frantz RP, McGoon MD, Hsiao JF, Maalouf JF, et al. Right ventricular strain for prediction of survival in patients with pulmonary arterial hypertension. Chest 2011;139: 1299-1309.
25. Hardegree EL, Sachdev A, Villarraga HR, Frantz RP, McGoon MD, Kushwaha SS, et al. Role of serial quantitative assessment of right ventricular function by strain in pulmonary arterial hypertension. Am J Cardiol 2013;111:143-148.
26. Oikawa M, Kagaya Y, Otani H, Sakuma M, Demachi J, Suzuki J, et al. Increased [18F]fluorodeoxyglucose accumulation in right ventricular free wall in patients with pulmonary hypertension and the effect of epoprostenol. J Am Coll Cardiol 2005;45:1849-1855.
27. Can MM, Kaymaz C, Tanboga IH, Tokgoz HC, Canpolat N, Turkyilmaz E, et al. Increased right ventricular glucose metabolism in patients with pulmonary arterial hypertension. Clin Nucl Med 2011;36:743-748.
28. Kawut SM, Lima JAC, Barr RG, Chahal H, Jain A, Tandri H, et al. Sex and race differences in right ventricular structure and function: The multi-ethnic study of atherosclerosis-right ventricle study. Circulation 2011;123:2542-2551.
29. Ventetuolo CE, Barr RG, Bluemke DA, Jain A, Delaney JA, Hundley WG, et al. Selective serotonin reuptake inhibitor use is associated with right ventricular structure and function: The MESA-right ventricle study. PLoS One 2012;7:e30480.
30. Ventetuolo CE, Ouyang P, Bluemke DA, Tandri H, Barr RG, Bagiella E, et al. Sex hormones are associated with right ventricular structure and function: The MESA-right ventricle study. Am J Respir Crit Care Med 2011;183:659-667.
31. Aaron CP, Tandri H, Barr RG, Johnson WC, Bagiella E, Chahal H, et al. Physical activity and right ventricular structure and function: The MESA-Right Ventricle Study. Am J Respir Crit Care Med 2011;183: 396-404.
32. Foppa M, Arora G, Gona P, Ashrafi A, Salton CJ, Yeon SB, et al. Right ventricular volumes and systolic function by cardiac magnetic resonance and the impact of sex, age, and obesity in a longitudinally followed cohort free of pulmonary and cardiovascular disease: The Framingham Heart Study. Circ Cardiovasc Imaging 2016;9:e003810.
33. Hudsmith LE, Petersen SE, Francis JM, Robson MD, Neubauer S. Normal human left and right ventricular and left atrial dimensions using steady state free precession magnetic resonance imaging. J Cardiovasc Magn Reson 2005;7:775-782.
34. Maceira AM, Prasad SK, Khan M, Pennell DJ. Reference right ventricular systolic and diastolic function normalized to age, gender and body surface area from steady-state free precession cardiovascular magnetic resonance. Eur Heart J 2006;27: 2879-2888.
35. Alfakih K, Plein S, Thiele H, Jones T, Ridgway JP, Sivananthan MU. Normal human left and right ventricular dimensions for MRI as assessed by turbo gradient echo and steady-state free precession imaging sequences. J Magn Reson Imaging 2003;17:323-329.
36. Leary PJ, Kaufman JD, Barr RG, Bluemke DA, Curl CL, Hough CL, et al. Traffic-related air pollution and the right ventricle: The Multi-Ethnic Study of Atherosclerosis. Am J Respir Crit Care Med 2014;189: 1093-1100.
37. Talwar A, Garcia JGN, Tsai H, Moreno M, Lahm T, Zamanian RT, et al.; Pulmonary Circulation Assembly. Health disparities in patients with pulmonary arterial hypertension: A blueprint for action. An Official American Thoracic Society statement. Am J Respir Crit Care Med 2017;196:e32-e47.
38. Lewandowski AJ, Bradlow WM, Augustine D, Davis EF, Francis J, Singhal A, et al. Right ventricular systolic dysfunction in young adults born preterm. Circulation 2013;128:713-720.
39. Goss KN, Cucci AR, Fisher AJ, Albrecht M, Frump A, Tursunova R, et al. Neonatal hyperoxic lung injury favorably alters adult right ventricular remodeling response to chronic hypoxia exposure. Am J Physiol Lung Cell Mol Physiol 2015;308:L797-L806.
40. Goss KN, Kumari S, Tetri LH, Barton G, Braun RK, Hacker TA, et al. Postnatal hyperoxia exposure durably impairs right ventricular function and mitochondrial biogenesis. Am J Respir Cell Mol Biol 2017;56:609-619.
41. Fleming TR, DeMets DL. Surrogate end points in clinical trials: Are we being misled?. Ann Intern Med 1996;125:605-613.
42. Buyse M, Molenberghs G. Criteria for the validation of surrogate endpoints in randomized experiments. Biometrics 1998;54:1014-1029.
43. Freedman LS, Graubard BI, Schatzkin A. Statistical validation of intermediate endpoints for chronic diseases. Stat Med 1992;11: 167-178.
44. Ventetuolo CE, Gabler NB, Fritz JS, Smith KA, Palevsky HI, Klinger JR, et al. Are hemodynamics surrogate end points in pulmonary arterial hypertension?. Circulation 2014;130:768-775.
45. Gabler NB, French B, Strom BL, Palevsky HI, Taichman DB, Kawut SM, et al. Validation of 6-minute walk distance as a surrogate end point in pulmonary arterial hypertension trials. Circulation 2012;126:349-356.
46. Savarese G, Musella F, D'Amore C, Losco T, Marciano C, Gargiulo P, et al. Haemodynamics, exercise capacity and clinical events in pulmonary arterial hypertension. Eur Respir J 2013;42:414-424.
47. Savarese G, Paolillo S, Costanzo P, D'Amore C, Cecere M, Losco T, et al. Do changes of 6-minute walk distance predict clinical events in patients with pulmonary arterial hypertension? A meta-analysis of 22 randomized trials. J Am Coll Cardiol 2012;60:1192-1201.
48. Ventetuolo CE, Kawut SM. What's the (end) point?. Eur Respir J 2015; 45:853-854.
49. Fritz JS, Blair C, Oudiz RJ, Dufton C, Olschewski H, Despain D, et al. Baseline and follow-up 6-min walk distance and brain natriuretic peptide predict 2-year mortality in pulmonary arterial hypertension. Chest 2013;143:315-323.
50. Vélez-Martínez M, Ayers C, Mishkin JD, Bartolome SB, García CK, Torres F, et al. Association of cardiac troponin I with disease severity and outcomes in patients with pulmonary hypertension. Am J Cardiol 2013;111:1812-1817.
51. Leary PJ, Kurtz CE, Hough CL, Waiss MP, Ralph DD, Sheehan FH. Three-dimensional analysis of right ventricular shape and function in pulmonary hypertension. Pulm Circ 2012;2:34-40.
52. Ohyama Y, Ambale-Venkatesh B, Chamera E, Shehata ML, Corona-Villalobos CP, Zimmerman SL, et al. Comparison of strain measurement from multimodality tissue tracking with strainencoding MRI and harmonic phase MRI in pulmonary hypertension. Int J Cardiol 2015;182:342-348.
53. Wilkins MR, Paul GA, Strange JW, Tunariu N, Gin-Sing W, Banya WA, et al. Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) study. Am J Respir Crit Care Med 2005;171: 1292-1297.
54. Chin KM, Kingman M, de Lemos JA, Warner JJ, Reimold S, Peshock R, et al. Changes in right ventricular structure and function assessed using cardiac magnetic resonance imaging in bosentan-treated patients with pulmonary arterial hypertension. Am J Cardiol 2008; 101:1669-1672.
55. Wilkins MR, Ali O, Bradlow W, Wharton J, Taegtmeyer A, Rhodes CJ, et al.; Simvastatin Pulmonary Hypertension Trial (SiPHT) Study Group. Simvastatin as a treatment for pulmonary hypertension trial. Am J Respir Crit Care Med 2010;181:1106-1113.
56. Hassoun PM, Zamanian RT, Damico R, Lechtzin N, Khair R, Kolb TM, et al. Ambrisentan and tadalafil up-front combination therapy in scleroderma-associated pulmonary arterial hypertension. Am J Respir Crit Care Med 2015;192:1102-1110.
57. Mercurio V, Mukherjee M, Tedford RJ, Zamanian RT, Khair RM, Sato T, et al. Improvement in right ventricular strain with ambrisentan and tadalafil upfront therapy in scleroderma-associated pulmonary arterial hypertension. Am J Respir Crit Care Med 2018;197:388-391.
58. Gan CT, Holverda S, Marcus JT, Paulus WJ, Marques KM, Bronzwaer JG, et al. Right ventricular diastolic dysfunction and the acute effects of sildenafil in pulmonary hypertension patients. Chest 2007;132: 11-17.
59. Rich S. The effects of vasodilators in pulmonary hypertension: Pulmonary vascular or peripheral vascular?. Circ Heart Fail 2009;2: 145-150.
60. Addetia K, Bhave NM, Tabit CE, Gomberg-Maitland M, Freed BH, Dill KE, et al. Sample size and cost analysis for pulmonary arterial hypertension drug trials using various imaging modalities to assess right ventricular size and function end points. Circ Cardiovasc Imaging 2014;7:115-124.
61. Galiè N, Barberà JA, Frost AE, Ghofrani HA, Hoeper MM, McLaughlin VV, et al.; AMBITION Investigators. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med 2015;373: 834-844.
62. Pulido T, Adzerikho I, Channick RN, Delcroix M, Galiè N, Ghofrani HA, et al.; SERAPHIN Investigators. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med 2013;369: 809-818.
63. Maarman G, Lecour S, Butrous G, Thienemann F, Sliwa K. A comprehensive review: The evolution of animal models in pulmonary hypertension research; are we there yet?. Pulm Circ 2013;3:739-756.
64. Stenmark KR, Meyrick B, Galie N, Mooi WJ, McMurtry IF. Animal models of pulmonary arterial hypertension: The hope for etiological discovery and pharmacological cure. Am J Physiol Lung Cell Mol Physiol 2009;297:L1013-L1032.
65. Bogaard HJ, Natarajan R, Henderson SC, Long CS, Kraskauskas D, Smithson L, et al. Chronic pulmonary artery pressure elevation is insufficient to explain right heart failure. Circulation 2009;120: 1951-1960.
66. Kerbaul F, Brimioulle S, Rondelet B, Dewachter C, Hubloue I, Naeije R. How prostacyclin improves cardiac output in right heart failure in conjunction with pulmonary hypertension. Am J Respir Crit Care Med 2007;175:846-850.
67. Bruns DR, Brown RD, Stenmark KR, Buttrick PM, Walker LA. Mitochondrial integrity in a neonatal bovine model of right ventricular dysfunction. Am J Physiol Lung Cell Mol Physiol 2015;308:L158-L167.
68. Kitahori K, He H, Kawata M, Cowan DB, Friehs I, Del Nido PJ, et al. Development of left ventricular diastolic dysfunction with preservation of ejection fraction during progression of infant right ventricular hypertrophy. Circ Heart Fail 2009;2:599-607.
69. Hemnes AR, Brittain EL, Trammell AW, Fessel JP, Austin ED, Penner N, et al. Evidence for right ventricular lipotoxicity in heritable pulmonary arterial hypertension. Am J Respir Crit Care Med 2014; 189:325-334.
70. Bonnet S, Provencher S, Guignabert C, Perros F, Boucherat O, Schermuly RT, et al. Translating research into improved patient care in pulmonary arterial hypertension. Am J Respir Crit Care Med 2017; 195:583-595.
71. Nagendran J, Sutendra G, Paterson I, Champion HC, Webster L, Chiu B, et al. Endothelin axis is upregulated in human and rat right ventricular hypertrophy. Circ Res 2013;112:347-354.
72. Piao L, Fang YH, Cadete VJ, Wietholt C, Urboniene D, Toth PT, et al. The inhibition of pyruvate dehydrogenase kinase improves impaired cardiac function and electrical remodeling in two models of right ventricular hypertrophy: Resuscitating the hibernating right ventricle. J Mol Med (Berl) 2010;88:47-60.
73. Neto-Neves EM, Frump AL, Vayl A, Kline JA, Lahm T. Isolated heart model demonstrates evidence of contractile and diastolic dysfunction in right ventricles from rats with sugen/hypoxia-induced pulmonary hypertension. Physiol Rep 2017;5:e13438.
74. Strange G, Playford D, Stewart S, Deague JA, Nelson H, Kent A, et al. Pulmonary hypertension: Prevalence and mortality in the Armadale echocardiography cohort. Heart 2012;98:1805-1811.
75. Vachiéry JL, Adir Y, Barberà JA, Champion H, Coghlan JG, Cottin V, et al. Pulmonary hypertension due to left heart diseases. J Am Coll Cardiol 2013;62:D100-D108.
76. Seeger W, Adir Y, Barberà JA, Champion H, Coghlan JG, Cottin V, et al. Pulmonary hypertension in chronic lung diseases. J Am Coll Cardiol 2013;62:D109-D116.
77. Walker LA, Walker JS, Glazier A, Brown DR, Stenmark KR, Buttrick PM. Biochemical and myofilament responses of the right ventricle to severe pulmonary hypertension. Am J Physiol Heart Circ Physiol 2011;301:H832-H840.
78. Bogaard HJ, Vonk Noordegraaf A, Voelkel NF. Right heart failure in chronic lung diseases and pulmonary arterial hypertension. In: Crawford MH, DiMarco JP, Paulus WJ, editors. Cardiology, 3rd ed. St. Louis: Elsevier; 2009. pp. 1159-1169.
79. Weissmann N, Lobo B, Pichl A, Parajuli N, Seimetz M, Puig-Pey R, et al. Stimulation of soluble guanylate cyclase prevents cigarette smokeinduced pulmonary hypertension and emphysema. Am J Respir Crit Care Med 2014;189:1359-1373.
80. Kasahara Y, Tuder RM, Taraseviciene-Stewart L, Le Cras TD, Abman S, Hirth PK, et al. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest 2000;106: 1311-1319.
81. Taraseviciene-Stewart L, Kasahara Y, Alger L, Hirth P, Mc Mahon G, Waltenberger J, et al. Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death-dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension. FASEB J 2001;15:427-438.
82. Bryant AJ, Carrick RP, McConaha ME, Jones BR, Shay SD, Moore CS, et al. Endothelial HIF signaling regulates pulmonary fibrosisassociated pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2016;310:L249-L262.
83. Farkas L, Farkas D, Ask K, Möller A, Gauldie J, Margetts P, et al. VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats. J Clin Invest 2009;119: 1298-1311.
84. Milano G, Raucci A, Scopece A, Daniele R, Guerrini U, Sironi L, et al. Doxorubicin and trastuzumab regimen induces biventricular failure in mice. J Am Soc Echocardiogr 2014;27:568-579.
85. Santamore WP, Lynch PR, Heckman JL, Bove AA, Meier GD. Left ventricular effects on right ventricular developed pressure. J Appl Physiol 1976;41:925-930.
86. Toldo S, Bogaard HJ, Van Tassell BW, Mezzaroma E, Seropian IM, Robati R, et al. Right ventricular dysfunction following acute myocardial infarction in the absence of pulmonary hypertension in the mouse. PLoS One 2011;6:e18102.
87. Chen Y, Guo H, Xu D, Xu X, Wang H, Hu X, et al. Left ventricular failure produces profound lung remodeling and pulmonary hypertension in mice: Heart failure causes severe lung disease. Hypertension 2012; 59:1170-1178.
88. Aguero J, Ishikawa K, Hadri L, Santos-Gallego C, Fish K, Hammoudi N, et al. Characterization of right ventricular remodeling and failure in a chronic pulmonary hypertension model. Am J Physiol Heart Circ Physiol 2014;307:H1204-H1215.
89. Lai YC, Tabima DM, Dube JJ, Hughan KS, Vanderpool RR, Goncharov DA, et al. SIRT3-AMP-activated protein kinase activation by nitrite and metformin improves hyperglycemia and normalizes pulmonary hypertension associated with heart failure with preserved ejection fraction. Circulation 2016;133:717-731.
90. Meng Q, Lai YC, Kelly NJ, Bueno M, Baust JJ, Bachman TN, et al. Development of a mouse model of metabolic syndrome, pulmonary hypertension, and heart failure with preserved ejection fraction. Am J Respir Cell Mol Biol 2017;56:497-505.
91. Smulders YM. Pathophysiology and treatment of haemodynamic instability in acute pulmonary embolism: The pivotal role of pulmonary vasoconstriction. Cardiovasc Res 2000;48:23-33.
92. Gold FL, Bache RJ. Transmural right ventricular blood flow during acute pulmonary artery hypertension in the sedated dog: Evidence for subendocardial ischemia despite residual vasodilator reserve. Circ Res 1982;51:196-204.
93. Sharma GV, Sasahara AA. Regional and transmural myocardial blood flow studies in experimental pulmonary embolism. Prog Cardiovasc Dis 1974;17:191-198.
94. Lahm T, McCaslin CA, Wozniak TC, Ghumman W, Fadl YY, Obeidat OS, et al. Medical and surgical treatment of acute right ventricular failure. J Am Coll Cardiol 2010;56:1435-1446.
95. Watts JA, Gellar MA, Obraztsova M, Kline JA, Zagorski J. Role of inflammation in right ventricular damage and repair following experimental pulmonary embolism in rats. Int J Exp Pathol 2008;89: 389-399.
96. Watts JA, Marchick MR, Kline JA. Right ventricular heart failure from pulmonary embolism: Key distinctions from chronic pulmonary hypertension. J Card Fail 2010;16:250-259.
97. Iwadate K, Tanno K, Doi M, Takatori T, Ito Y. Two cases of right ventricular ischemic injury due to massive pulmonary embolism. Forensic Sci Int 2001;116:189-195.
98. Watts JA, Zagorski J, Gellar MA, Stevinson BG, Kline JA. Cardiac inflammation contributes to right ventricular dysfunction following experimental pulmonary embolism in rats. J Mol Cell Cardiol 2006; 41:296-307.
99. Zagorski J, Obraztsova M, Gellar MA, Kline JA, Watts JA. Transcriptional changes in right ventricular tissues are enriched in the outflow tract compared with the apex during chronic pulmonary embolism in rats. Physiol Genomics 2009;39:61-71.
100. Zagorski J, Gellar MA, Obraztsova M, Kline JA, Watts JA. Inhibition of CINC-1 decreases right ventricular damage caused by experimental pulmonary embolism in rats. J Immunol 2007;179: 7820-7826.
101. Iwadate K, Doi M, Tanno K, Katsumura S, Ito H, Sato K, et al. Right ventricular damage due to pulmonary embolism: Examination of the number of infiltrating macrophages. Forensic Sci Int 2003;134: 147-153.
102. Sullivan DM, Watts JA, Kline JA. Biventricular cardiac dysfunction after acute massive pulmonary embolism in the rat. J Appl Physiol (1985) 2001;90:1648-1656.
103. Gurudevan SV, Malouf PJ, Auger WR, Waltman TJ, Madani M, Raisinghani AB, et al. Abnormal left ventricular diastolic filling in chronic thromboembolic pulmonary hypertension: True diastolic dysfunction or left ventricular underfilling?. J Am Coll Cardiol 2007; 49:1334-1339.
104. Amà R, Leather HA, Segers P, Vandermeersch E, Wouters PF. Acute pulmonary hypertension causes depression of left ventricular contractility and relaxation. Eur J Anaesthesiol 2006;23:824-831.
105. Pengo V, Lensing AW, Prins MH, Marchiori A, Davidson BL, Tiozzo F, et al.; Thromboembolic Pulmonary Hypertension Study Group. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 2004; 350:2257-2264.
106. Mekontso Dessap A, Boissier F, Charron C, Bégot E, Repessé X, Legras A, et al. Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: Prevalence, predictors, and clinical impact. Intensive Care Med 2016;42:862-870.
107. Vieillard-Baron A, Matthay M, Teboul JL, Bein T, Schultz M, Magder S, et al. Experts' opinion on management of hemodynamics in ARDS patients: Focus on the effects of mechanical ventilation. Intensive Care Med 2016;42:739-749.
108. Guérin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, et al.; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013;368:2159-2168.
109. Vieillard-Baron A, Charron C, Caille V, Belliard G, Page B, Jardin F. Prone positioning unloads the right ventricle in severe ARDS. Chest 2007;132:1440-1446.
110. Sista AK, Goldhaber SZ, Vedantham S, Kline JA, Kuo WT, Kahn SR, et al. Research priorities in submassive pulmonary embolism: Proceedings from a multidisciplinary research consensus panel. J Vasc Interv Radiol 2016;27:787-794.
111. Piao L, Fang YH, Parikh KS, Ryan JJ, D'Souza KM, Theccanat T, et al. GRK2-mediated inhibition of adrenergic and dopaminergic signaling in right ventricular hypertrophy: Therapeutic implications in pulmonary hypertension. Circulation 2012;126:2859-2869.
112. Campo A, Mathai SC, Le Pavec J, Zaiman AL, Hummers LK, Boyce D, et al. Outcomes of hospitalisation for right heart failure in pulmonary arterial hypertension. Eur Respir J 2011;38:359-367.
113. Neto-Neves EM, Brown MB, Zaretskaia MV, Rezania S, Goodwill AG, McCarthy BP, et al. Chronic embolic pulmonary hypertension caused by pulmonary embolism and vascular endothelial growth factor inhibition. Am J Pathol 2017;187:700-712.
114. Noly PE, Guihaire J, Coblence M, Dorfmüller P, Fadel E, Mercier O. Chronic thromboembolic pulmonary hypertension and assessment of right ventricular function in the piglet. J Vis Exp 2015;105:e53133.
115. Guihaire J, Haddad F, Noly PE, Boulate D, Decante B, Dartevelle P, et al. Right ventricular reserve in a piglet model of chronic pulmonary hypertension. Eur Respir J 2015;45:709-717.
116. Mekontso Dessap A, Voiriot G, Zhou T, Marcos E, Dudek SM, Jacobson JR, et al. Conflicting physiological and genomic cardiopulmonary effects of recruitment maneuvers in murine acute lung injury. Am J Respir Cell Mol Biol 2012;46:541-550.
117. van de Veerdonk MC, Bogaard HJ, Voelkel NF. The right ventricle and pulmonary hypertension. Heart Fail Rev 2016;21:259-271.
118. Ryan JJ, Archer SL. The right ventricle in pulmonary arterial hypertension: Disorders of metabolism, angiogenesis and adrenergic signaling in right ventricular failure. Circ Res 2014;115: 176-188.
119. Bogaard HJ, Abe K, Vonk Noordegraaf A, Voelkel NF. The right ventricle under pressure: Cellular and molecular mechanisms of right-heart failure in pulmonary hypertension. Chest 2009;135:794-804.
120. Drake JI, Bogaard HJ, Mizuno S, Clifton B, Xie B, Gao Y, et al. Molecular signature of a right heart failure program in chronic severe pulmonary hypertension. Am J Respir Cell Mol Biol 2011;45: 1239-1247.
121. Vogel-Claussen J, Skrok J, Shehata ML, Singh S, Sibley CT, Boyce DM, et al. Right and left ventricular myocardial perfusion reserves correlate with right ventricular function and pulmonary hemodynamics in patients with pulmonary arterial hypertension. Radiology 2011;258:119-127.
122. Fang YH, Piao L, Hong Z, Toth PT, Marsboom G, Bache-Wiig P, et al. Therapeutic inhibition of fatty acid oxidation in right ventricular hypertrophy: Exploiting Randle's cycle. J MolMed (Berl) 2012;90:31-43.
123. Piao L, Sidhu VK, Fang YH, Ryan JJ, Parikh KS, Hong Z, et al. FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 (PDK4) decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension: Therapeutic benefits of dichloroacetate. J Mol Med (Berl) 2013;91:333-346.
124. Piao L, Fang YH, Parikh K, Ryan JJ, Toth PT, Archer SL. Cardiac glutaminolysis: A maladaptive cancer metabolism pathway in the right ventricle in pulmonary hypertension. J Mol Med (Berl) 2013;91: 1185-1197.
125. Helms CC, Marvel M, Zhao W, Stahle M, Vest R, Kato GJ, et al. Mechanisms of hemolysis-associated platelet activation. J Thromb Haemost 2013;11:2148-2154.
126. Kline JA, Marchick MR, Hogg MM. Reduction in plasma haptoglobin in humans with acute pulmonary embolism causing tricuspid regurgitation. J Thromb Haemost 2009;7:1597-1599.
127. Insenser M, Montes-Nieto R, Martínez-García MA, Durán EF, Santiuste C, Gómez V, et al. Identification of reduced circulating haptoglobin concentration as a biomarker of the severity of pulmonary embolism: A nontargeted proteomic study. PLoS One 2014;9:e100902.
128. Vonk Noordegraaf A, Westerhof BE, Westerhof N. The relationship between the right ventricle and its load in pulmonary hypertension. J Am Coll Cardiol 2017;69:236-243.
129. Swift AJ, Capener D, Johns C, Hamilton N, Rothman A, Elliot C, et al. Magnetic resonance imaging in the prognostic evaluation of patients with pulmonary arterial hypertension. Am J Respir Crit Care Med 2017;196:228-239.
130. Haddad F, Spruijt OA, Denault AY, Mercier O, Brunner N, Furman D, et al. Right heart score for predicting outcome in idiopathic, familial, or drug- and toxin-associated pulmonary arterial hypertension. JACC Cardiovasc Imaging 2015;8:627-638.
131. Fuster V, Steele PM, Edwards WD, Gersh BJ, McGoon MD, Frye RL. Primary pulmonary hypertension: natural history and the importance of thrombosis. Circulation 1984;70:580-587.
132. D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, et al. Survival in patients with primary pulmonary hypertension: Results from a national prospective registry. Ann Intern Med 1991; 115:343-349.
133. Sandoval J, Bauerle O, Palomar A, Gómez A, Martínez-Guerra ML, Beltrán M, et al. Survival in primary pulmonary hypertension: Validation of a prognostic equation. Circulation 1994;89:1733-1744.
134. McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: The impact of epoprostenol therapy. Circulation 2002; 106:1477-1482.
135. Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, et al. Survival in patients with idiopathic, familial, and anorexigenassociated pulmonary arterial hypertension in the modern management era. Circulation 2010;122:156-163.
136. Benza RL, Miller DP, Gomberg-Maitland M, Frantz RP, Foreman AJ, Coffey CS, et al. Predicting survival in pulmonary arterial hypertension: Insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation 2010;122:164-172.
137. Sitbon O, Humbert M, Nunes H, Parent F, Garcia G, Hervé P, et al. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: Prognostic factors and survival. J Am Coll Cardiol 2002;40:780-788.
138. Eysmann SB, Palevsky HI, Reichek N, Hackney K, Douglas PS. Two-dimensional and Doppler-echocardiographic and cardiac catheterization correlates of survival in primary pulmonary hypertension. Circulation 1989;80:353-360.
139. Raymond RJ, Hinderliter AL, Willis PW, Ralph D, Caldwell EJ, Williams W, et al. Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension. J Am Coll Cardiol 2002;39: 1214-1219.
140. Brierre G, Blot-Souletie N, Degano B, Têtu L, Bongard V, Carrié D. New echocardiographic prognostic factors for mortality in pulmonary arterial hypertension. Eur J Echocardiogr 2010;11:516-522.
141. Fine NM, Chen L, Bastiansen PM, Frantz RP, Pellikka PA, Oh JK, et al. Outcome prediction by quantitative right ventricular function assessment in 575 subjects evaluated for pulmonary hypertension. Circ Cardiovasc Imaging 2013;6:711-721.
142. Bustamante-Labarta M, Perrone S, De La Fuente RL, Stutzbach P, De La Hoz RP, Torino A, et al. Right atrial size and tricuspid regurgitation severity predict mortality or transplantation in primary pulmonary hypertension. J Am Soc Echocardiogr 2002;15:1160-1164.
143. Ghio S, Klersy C, Magrini G, D'Armini AM, Scelsi L, Raineri C, et al. Prognostic relevance of the echocardiographic assessment of right ventricular function in patients with idiopathic pulmonary arterial hypertension. Int J Cardiol 2010;140:272-278.
144. Ghio S, Pazzano AS, Klersy C, Scelsi L, Raineri C, Camporotondo R, et al. Clinical and prognostic relevance of echocardiographic evaluation of right ventricular geometry in patients with idiopathic pulmonary arterial hypertension. Am J Cardiol 2011;107:628-632.
145. Utsunomiya H, Nakatani S, Nishihira M, Kanzaki H, Kyotani S, Nakanishi N, et al. Value of estimated right ventricular filling pressure in predicting cardiac events in chronic pulmonary arterial hypertension. J Am Soc Echocardiogr 2009;22:1368-1374.
146. Ameloot K, Palmers PJ, Vande Bruaene A, Gerits A, Budts W, Voigt JU, et al. Clinical value of echocardiographic Doppler-derived right ventricular dp/dt in patients with pulmonary arterial hypertension. Eur Heart J Cardiovasc Imaging 2014;15:1411-1419.
147. Ernande L, Cottin V, Leroux PY, Girerd N, Huez S, Mulliez A, et al. Right isovolumic contraction velocity predicts survival in pulmonary hypertension. J Am Soc Echocardiogr 2013;26:297-306.
148. Haeck ML, Scherptong RW, Marsan NA, Holman ER, Schalij MJ, Bax JJ, et al. Prognostic value of right ventricular longitudinal peak systolic strain in patients with pulmonary hypertension. Circ Cardiovasc Imaging 2012;5:628-636.
149. Smith BC, Dobson G, Dawson D, Charalampopoulos A, Grapsa J, Nihoyannopoulos P. Three-dimensional speckle tracking of the right ventricle: Toward optimal quantification of right ventricular dysfunction in pulmonary hypertension. J Am Coll Cardiol 2014;64: 41-51.
150. Badagliacca R, Poscia R, Pezzuto B, Papa S, Gambardella C, Francone M, et al. Right ventricular dyssynchrony in idiopathic pulmonary arterial hypertension: Determinants and impact on pump function. J Heart Lung Transplant 2015;34:381-389.
151. Tei C, Dujardin KS, Hodge DO, Bailey KR, McGoon MD, Tajik AJ, et al. Doppler echocardiographic index for assessment of global right ventricular function. J Am Soc Echocardiogr 1996;9:838-847.
152. Yeo TC, Dujardin KS, Tei C, Mahoney DW, McGoon MD, Seward JB. Value of a Doppler-derived index combining systolic and diastolic time intervals in predicting outcome in primary pulmonary hypertension. Am J Cardiol 1998;81:1157-1161.
153. Grünig E, Tiede H, Enyimayew EO, Ehlken N, Seyfarth HJ, Bossone E, et al. Assessment and prognostic relevance of right ventricular contractile reserve in patients with severe pulmonary hypertension. Circulation 2013;128:2005-2015.
154. Moledina S, Pandya B, Bartsota M, Mortensen KH, McMillan M, Quyam S, et al. Prognostic significance of cardiac magnetic resonance imaging in children with pulmonary hypertension. Circ Cardiovasc Imaging 2013;6:407-414.
155. Yamada Y, Okuda S, Kataoka M, Tanimoto A, Tamura Y, Abe T, et al. Prognostic value of cardiac magnetic resonance imaging for idiopathic pulmonary arterial hypertension before initiating intravenous prostacyclin therapy. Circ J 2012;76:1737-1743.
156. Brewis MJ, Bellofiore A, Vanderpool RR, Chesler NC, Johnson MK, Naeije R, et al. Imaging right ventricular function to predict outcome in pulmonary arterial hypertension. Int J Cardiol 2016; 218:206-211.
157. Swift AJ, Rajaram S, Campbell MJ, Hurdman J, Thomas S, Capener D, et al. Prognostic value of cardiovascular magnetic resonance imaging measurements corrected for age and sex in idiopathic pulmonary arterial hypertension. Circ Cardiovasc Imaging 2014;7: 100-106.
158. Freed BH, Gomberg-Maitland M, Chandra S, Mor-Avi V, Rich S, Archer SL, et al. Late gadolinium enhancement cardiovascular magnetic resonance predicts clinical worsening in patients with pulmonary hypertension. J Cardiovasc Magn Reson 2012;14:11.
159. Swift AJ, Rajaram S, Capener D, Elliot C, Condliffe R, Wild JM, et al. LGE patterns in pulmonary hypertension do not impact overall mortality. JACC Cardiovasc Imaging 2014;7:1209-1217.
160. Dawes TJW, de Marvao A, Shi W, Fletcher T, Watson GMJ, Wharton J, et al. Machine learning of three-dimensional right ventricular motion enables outcome prediction in pulmonary hypertension: A cardiac MR imaging study. Radiology 2017;283: 381-390.
161. Vonk-Noordegraaf A, Westerhof N. Describing right ventricular function. Eur Respir J 2013;41:1419-1423.
162. Kussmaul WG, Noordergraaf A, Laskey WK. Right ventricularpulmonary arterial interactions. Ann Biomed Eng 1992;20:63-80.
163. Suga H, Sagawa K, Shoukas AA. Load independence of the instantaneous pressure-volume ratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio. Circ Res 1973;32: 314-322.
164. Maughan WL, Shoukas AA, Sagawa K, Weisfeldt ML. Instantaneous pressure-volume relationship of the canine right ventricle. Circ Res 1979;44:309-315.
165. Sagawa K, Maughan L, Suga H, Sunagawa K. Cardiac contraction and the pressure-volume relationship. New York: Oxford Unversity Press; 1988.
166. Spruijt OA, de Man FS, Groepenhoff H, Oosterveer F, Westerhof N, Vonk-Noordegraaf A, et al. The effects of exercise on right ventricular contractility and right ventricular-arterial coupling in pulmonary hypertension. Am J Respir Crit Care Med 2015;191: 1050-1057.
167. Hsu S, Houston BA, Tampakakis E, Bacher AC, Rhodes PS, Mathai SC, et al. Right ventricular functional reserve in pulmonary arterial hypertension. Circulation 2016;133:2413-2422.
168. Fourie PR, Coetzee AR, Bolliger CT. Pulmonary artery compliance: Its role in right ventricular-arterial coupling. Cardiovasc Res 1992;26: 839-844.
169. Ghuysen A, Lambermont B, Kolh P, Tchana-Sato V, Magis D, Gerard P, et al. Alteration of right ventricular-pulmonary vascular coupling in a porcine model of progressive pressure overloading. Shock 2008;29: 197-204.
170. Tedford RJ, Mudd JO, Girgis RE, Mathai SC, Zaiman AL, Housten-Harris T, et al. Right ventricular dysfunction in systemic sclerosisassociated pulmonary arterial hypertension. Circ Heart Fail 2013;6: 953-963.
171. Mahapatra S, Nishimura RA, Oh JK, McGoon MD. The prognostic value of pulmonary vascular capacitance determined by Doppler echocardiography in patients with pulmonary arterial hypertension. J Am Soc Echocardiogr 2006;19:1045-1050.
172. Gan CT, Lankhaar JW, Westerhof N, Marcus JT, Becker A, Twisk JW, et al. Noninvasively assessed pulmonary artery stiffness predicts mortality in pulmonary arterial hypertension. Chest 2007;132:1906-1912.
173. Tabima DM, Roldan-Alzate A, Wang Z, Hacker TA, Molthen RC, Chesler NC. Persistent vascular collagen accumulation alters hemodynamic recovery from chronic hypoxia. J Biomech 2012;45: 799-804.
174. Ooi CY, Wang Z, Tabima DM, Eickhoff JC, Chesler NC. The role of collagen in extralobar pulmonary artery stiffening in response to hypoxia-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol 2010;299:H1823-H1831.
175. Stevens GR, Garcia-Alvarez A, Sahni S, Garcia MJ, Fuster V, Sanz J. RV dysfunction in pulmonary hypertension is independently related to pulmonary artery stiffness. JACC Cardiovasc Imaging 2012;5: 378-387.
176. Brimioulle S, Wauthy P, Ewalenko P, Rondelet B, Vermeulen F, Kerbaul F, et al. Single-beat estimation of right ventricular endsystolic pressure-volume relationship. Am J Physiol Heart Circ Physiol 2003;284:H1625-H1630.
177. Kuehne T, Yilmaz S, Steendijk P, Moore P, Groenink M, Saaed M, et al. Magnetic resonance imaging analysis of right ventricular pressure-volume loops: In vivo validation and clinical application in patients with pulmonary hypertension. Circulation 2004;110: 2010-2016.
178. Wauthy P, Naeije R, Brimioulle S. Left and right ventriculo-arterial coupling in a patient with congenitally corrected transposition. Cardiol Young 2005;15:647-649.
179. McCabe C, White PA, Hoole SP, Axell RG, Priest AN, Gopalan D, et al. Right ventricular dysfunction in chronic thromboembolic obstruction of the pulmonary artery: A pressure-volume study using the conductance catheter. J Appl Physiol (1985) 2014;116: 355-363.
180. Sanz J, García-Alvarez A, Fernández-Friera L, Nair A, Mirelis JG, Sawit ST, et al. Right ventriculo-arterial coupling in pulmonary hypertension: A magnetic resonance study. Heart 2012;98: 238-243.
181. Trip P, Kind T, van de Veerdonk MC, Marcus JT, de Man FS, Westerhof N, et al. Accurate assessment of load-independent right ventricular systolic function in patients with pulmonary hypertension. J Heart Lung Transplant 2013;32:50-55.
182. Rain S, Handoko ML, Trip P, Gan CT, Westerhof N, Stienen GJ, et al. Right ventricular diastolic impairment in patients with pulmonary arterial hypertension. Circulation 2013;128:2016-2025.
183. Trip P, Rain S, Handoko ML, van der Bruggen C, Bogaard HJ, Marcus JT, et al. Clinical relevance of right ventricular diastolic stiffness in pulmonary hypertension. Eur Respir J 2015;45:1603-1612.
184. Vanderpool RR, Pinsky MR, Naeije R, Deible C, Kosaraju V, Bunner C, et al. RV-pulmonary arterial coupling predicts outcome in patients referred for pulmonary hypertension. Heart 2015;101:37-43.
185. Santamore WP, Dell'Italia LJ. Ventricular interdependence: Significant left ventricular contributions to right ventricular systolic function. Prog Cardiovasc Dis 1998;40:289-308.
186. Lazar JM, Flores AR, Grandis DJ, Orie JE, Schulman DS. Effects of chronic right ventricular pressure overload on left ventricular diastolic function. Am J Cardiol 1993;72:1179-1182.
187. Belenkie I, Horne SG, Dani R, Smith ER, Tyberg JV. Effects of aortic constriction during experimental acute right ventricular pressure loading: Further insights into diastolic and systolic ventricular interaction. Circulation 1995;92:546-554.
188. van Wolferen SA, Marcus JT, Westerhof N, Spreeuwenberg MD, Marques KM, Bronzwaer JG, et al. Right coronary artery flow impairment in patients with pulmonary hypertension. Eur Heart J 2008;29:120-127.
189. Marcus JT, Gan CT, Zwanenburg JJ, Boonstra A, Allaart CP, Götte MJ, et al. Interventricular mechanical asynchrony in pulmonary arterial hypertension: Left-to-right delay in peak shortening is related to right ventricular overload and left ventricular underfilling. J Am Coll Cardiol 2008;51:750-757.
190. Rich JD, Thenappan T, Freed B, Patel AR, Thisted RA, Childers R, et al. QTc prolongation is associated with impaired right ventricular function and predicts mortality in pulmonary hypertension. Int J Cardiol 2013;167:669-676.
191. van der Bruggen CE, Happé CM, Dorfmüller P, Trip P, Spruijt OA, Rol N, et al. Bone morphogenetic protein receptor type 2 mutation in pulmonary arterial hypertension: A view on the right ventricle. Circulation 2016;133:1747-1760.
192. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature 2011;473:298-307.
193. Oka T, Akazawa H, Naito AT, Komuro I. Angiogenesis and cardiac hypertrophy: Maintenance of cardiac function and causative roles in heart failure. Circ Res 2014;114:565-571.
194. Walsh K, Shiojima I. Cardiac growth and angiogenesis coordinated by intertissue interactions. J Clin Invest 2007;117:3176-3179.
195. Heineke J, Auger-Messier M, Xu J, Oka T, Sargent MA, York A, et al. Cardiomyocyte GATA4 functions as a stress-responsive regulator of angiogenesis in the murine heart. J Clin Invest 2007;117:3198-3210.
196. Shiojima I, Sato K, Izumiya Y, Schiekofer S, Ito M, Liao R, et al. Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure. J Clin Invest 2005;115: 2108-2118.
197. Jaba IM, Zhuang ZW, Li N, Jiang Y, Martin KA, Sinusas AJ, et al. NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth. J Clin Invest 2013;123:1718-1731.
198. Tirziu D, Chorianopoulos E, Moodie KL, Palac RT, Zhuang ZW, Tjwa M, et al. Myocardial hypertrophy in the absence of external stimuli is induced by angiogenesis in mice. J Clin Invest 2007;117: 3188-3197.
199. Zong P, Tune JD, Downey HF. Mechanisms of oxygen demand/supply balance in the right ventricle. Exp Biol Med (Maywood) 2005;230:507-519.
200. Frump AL, Bonnet S, de Jesus Perez VA, Lahm T. The emerging role of angiogenesis in adaptive and maladaptive right ventricular remodeling in pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2018;314:L443-L460.
201. Hudlicka O, Brown M, Egginton S. Angiogenesis in skeletal and cardiac muscle. Physiol Rev 1992;72:369-417.
202. Kaneko N, Matsuda R, Toda M, Shimamoto K. Three-dimensional reconstruction of the human capillary network and the intramyocardial micronecrosis. Am J Physiol Heart Circ Physiol 2011;300:H754-H761.
203. Kayar SR, Banchero N. Myocardial capillarity in acclimation to hypoxia. Pflugers Arch 1985;404:319-325.
204. Miller AT Jr, Hale DM. Increased vascularity of brain, heart, and skeletal muscle of polycythemic rats. Am J Physiol 1970;219:702-704.
205. Turek Z, Grandtner M, Kreuzer F. Cardiac hypertrophy, capillary and muscle fiber density, muscle fiber diameter, capillary radius and diffusion distance in the myocardium of growing rats adapted to a simulated altitude of 3500 m. Pflugers Arch 1972;335:19-28.
206. Clark DR, Smith P. Capillary density and muscle fibre size in the hearts of rats subjected to stimulated high altitude. Cardiovasc Res 1978; 12:578-584.
207. Partovian C, Adnot S, Eddahibi S, Teiger E, Levame M, Dreyfus P, et al. Heart and lung VEGF mRNA expression in rats with monocrotaline- or hypoxia-induced pulmonary hypertension. Am J Physiol 1998;275:H1948-H1956.
208. Turek Z, Hoofd LJ, Ringnalda BE, Rakusan K. Myocardial capillarity of rats exposed to simulated high altitude. Adv Exp Med Biol 1985; 191:249-255.
209. Sutendra G, Dromparis P, Paulin R, Zervopoulos S, Haromy A, Nagendran J, et al. A metabolic remodeling in right ventricular hypertrophy is associated with decreased angiogenesis and a transition from a compensated to a decompensated state in pulmonary hypertension. J Mol Med (Berl) 2013;91:1315-1327.
210. Gómez A, Bialostozky D, Zajarias A, Santos E, Palomar A, Martínez ML, et al. Right ventricular ischemia in patients with primary pulmonary hypertension. J Am Coll Cardiol 2001;38:1137-1142.
211. Graham BB, Koyanagi D, Kandasamy B, Tuder RM. Right ventricle vasculature in human pulmonary hypertension assessed by stereology. Am J Respir Crit Care Med 2017;196:1075-1077.
212. Chen JX, Stinnett A. Disruption of Ang-1/Tie-2 signaling contributes to the impaired myocardial vascular maturation and angiogenesis in type II diabetic mice. Arterioscler Thromb Vasc Biol 2008;28: 1606-1613.
213. Javan H, Szucsik AM, Li L, Schaaf CL, Salama ME, Selzman CH. Cardiomyocyte p65 nuclear factor-kB is necessary for compensatory adaptation to pressure overload. Circ Heart Fail 2015;8:109-118.
214. Kan J, Guo W, Huang C, Bao G, Zhu Y, Zhu YZ. S-propargyl-cysteine, a novel water-soluble modulator of endogenous hydrogen sulfide, promotes angiogenesis through activation of signal transducer and activator of transcription 3. Antioxid Redox Signal 2014;20:2303-2316.
215. Steagall RJ, Daniels CR, Dalal S, Joyner WL, Singh M, Singh K. Extracellular ubiquitin increases expression of angiogenic molecules and stimulates angiogenesis in cardiac microvascular endothelial cells. Microcirculation 2014;21:324-332.
216. Valcarcel-Ares MN, Gautam T, Warrington JP, Bailey-Downs L, Sosnowska D, de Cabo R, et al. Disruption of Nrf2 signaling impairs angiogenic capacity of endothelial cells: Implications for microvascular aging. J Gerontol A Biol Sci Med Sci 2012;67: 821-829.
217. Potus F, Ruffenach G, Dahou A, Thebault C, Breuils-Bonnet S, Tremblay È, et al. Downregulation of microRNA-126 contributes to the failing right ventricle in pulmonary arterial hypertension. Circulation 2015;132:932-943.
218. Damico R, Kolb TM, Valera L, Wang L, Housten T, Tedford RJ, et al. Serum endostatin is a genetically determined predictor of survival in pulmonary arterial hypertension. Am J Respir Crit Care Med 2015; 191:208-218.
219. Hoffmann J, Marsh LM, Pieper M, Stacher E, Ghanim B, Kovacs G, et al. Compartment-specific expression of collagens and their processing enzymes in intrapulmonary arteries of IPAH patients. Am J Physiol Lung Cell Mol Physiol 2015;308:L1002-L1013.
220. Al-Husseini A, Kraskauskas D, Mezzaroma E, Nordio A, Farkas D, Drake JI, et al. Vascular endothelial growth factor receptor 3 signaling contributes to angioobliterative pulmonary hypertension. Pulm Circ 2015;5:101-116.
221. Weibel ER, Hsia CC, Ochs M. How much is there really? Why stereology is essential in lung morphometry. J Appl Physiol (1985) 2007;102:459-467.
222. Bradley SP, Auger WR, Moser KM, Fedullo PF, Channick RN, Bloor CM. Right ventricular pathology in chronic pulmonary hypertension. Am J Cardiol 1996;78:584-587.
223. Frump AL, Goss KN, Vayl A, Albrecht M, Fisher A, Tursunova R, et al. Estradiol improves right ventricular function in rats with severe angioproliferative pulmonary hypertension: Effects of endogenous and exogenous sex hormones. Am J Physiol Lung Cell Mol Physiol 2015;308:L873-L890.
224. Wehman B, Sharma S, Pietris N, Mishra R, Siddiqui OT, Bigham G, et al. Mesenchymal stem cells preserve neonatal right ventricular function in a porcine model of pressure overload. Am J Physiol Heart Circ Physiol 2016;310:H1816-H1826.
225. Vonk Noordegraaf A, Haddad F, Bogaard HJ, Hassoun PM. Noninvasive imaging in the assessment of the cardiopulmonary vascular unit. Circulation 2015;131:899-913.
226. Sanz J, Dellegrottaglie S, Kariisa M, Sulica R, Poon M, O'Donnell TP, et al. Prevalence and correlates of septal delayed contrast enhancement in patients with pulmonary hypertension. Am J Cardiol 2007;100:731-735.
227. Spruijt OA, Vissers L, Bogaard HJ, Hofman MB, Vonk-Noordegraaf A, Marcus JT. Increased native T1-values at the interventricular insertion regions in precapillary pulmonary hypertension. Int J Cardiovasc Imaging 2016;32:451-459.
228. Liu H, Wu Y, Wang F, Liu Z. Molecular imaging of integrin avb6 expression in living subjects. Am J Nucl Med Mol Imaging 2014;4: 333-345.
229. Ryan JJ, Archer SL. Emerging concepts in the molecular basis of pulmonary arterial hypertension: Part I: Metabolic plasticity and mitochondrial dynamics in the pulmonary circulation and right ventricle in pulmonary arterial hypertension. Circulation 2015;131: 1691-1702.
230. Lopaschuk GD, Ussher JR, Folmes CD, Jaswal JS, Stanley WC. Myocardial fatty acid metabolism in health and disease. Physiol Rev 2010;90:207-258.
231. Piao L, Marsboom G, Archer SL. Mitochondrial metabolic adaptation in right ventricular hypertrophy and failure. J Mol Med (Berl) 2010; 88:1011-1020.
232. Graham BB, Kumar R, Mickael C, Sanders L, Gebreab L, Huber KM, et al. Severe pulmonary hypertension is associated with altered right ventricle metabolic substrate uptake. Am J Physiol Lung Cell Mol Physiol 2015;309:L435-L440.
233. Archer SL, Marsboom G, Kim GH, Zhang HJ, Toth PT, Svensson EC, et al. Epigenetic attenuation of mitochondrial superoxide dismutase 2 in pulmonary arterial hypertension: A basis for excessive cell proliferation and a new therapeutic target. Circulation 2010;121: 2661-2671.
234. Archer SL, Fang YH, Ryan JJ, Piao L. Metabolism and bioenergetics in the right ventricle and pulmonary vasculature in pulmonary hypertension. Pulm Circ 2013;3:144-152.
235. Ohira H, deKemp R, Pena E, Davies RA, Stewart DJ, Chandy G, et al. Shifts in myocardial fatty acid and glucose metabolism in pulmonary arterial hypertension: A potential mechanism for a maladaptive right ventricular response. Eur Heart J Cardiovasc Imaging 2016;17:1424-1431.
236. Wong YY, Raijmakers P, van Campen J, van der Laarse WJ, Knaapen P, Lubberink M, et al. 11C-Acetate clearance as an index of oxygen consumption of the right myocardium in idiopathic pulmonary arterial hypertension: A validation study using 15O-labeled tracers and PET. J Nucl Med 2013;54:1258-1262.
237. Fang W, Zhao L, Xiong CM, Ni XH, He ZX, He JG, et al. Comparison of 18F-FDG uptake by right ventricular myocardium in idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease. Pulm Circ 2012;2:365-372.
238. Bokhari S, Raina A, Rosenweig EB, Schulze PC, Bokhari J, Einstein AJ, et al. PET imaging may provide a novel biomarker and understanding of right ventricular dysfunction in patients with idiopathic pulmonary arterial hypertension. Circ Cardiovasc Imaging 2011;4:641-647.
239. Sakao S, Miyauchi H, Voelkel NF, Sugiura T, Tanabe N, Kobayashi Y, et al. Increased right ventricular fatty acid accumulation in chronic thromboembolic pulmonary hypertension. Ann Am Thorac Soc 2015;12:1465-1472.
240. Urboniene D, Haber I, Fang YH, Thenappan T, Archer SL. Validation of high-resolution echocardiography and magnetic resonance imaging vs. high-fidelity catheterization in experimental pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2010;299: L401-L412.
241. Malenfant S, Potus F, Mainguy V, Leblanc E, Malenfant M, Ribeiro F, et al. Impaired skeletal muscle oxygenation and exercise tolerance in pulmonary hypertension. Med Sci Sports Exerc 2015;47:2273-2282.
242. Malenfant S, Potus F, Fournier F, Breuils-Bonnet S, Pflieger A, Bourassa S, et al. Skeletal muscle proteomic signature and metabolic impairment in pulmonary hypertension. J Mol Med (Berl) 2015;93:573-584.
243. Batt J, Ahmed SS, Correa J, Bain A, Granton J. Skeletal muscle dysfunction in idiopathic pulmonary arterial hypertension. Am J Respir Cell Mol Biol 2014;50:74-86.
244. Heresi GA, Tang WH, Aytekin M, Hammel J, Hazen SL, Dweik RA. Sensitive cardiac troponin I predicts poor outcomes in pulmonary arterial hypertension. Eur Respir J 2012;39:939-944.
245. Gomez-Arroyo J, Sakagami M, Syed AA, Farkas L, Van Tassell B, Kraskauskas D, et al. Iloprost reverses established fibrosis in experimental right ventricular failure. Eur Respir J 2015;45:449-462.
246. Lahm T, Frump AL, Albrecht ME, Fisher AJ, Cook TG, Jones TJ, et al. 17b-Estradiol mediates superior adaptation of right ventricular function to acute strenuous exercise in female rats with severe pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2016; 311:L375-L388.
247. Rawat DK, Alzoubi A, Gupte R, Chettimada S, Watanabe M, Kahn AG, et al. Increased reactive oxygen species, metabolic maladaptation, and autophagy contribute to pulmonary arterial hypertensioninduced ventricular hypertrophy and diastolic heart failure. Hypertension 2014;64:1266-1274.
248. Szobi A, Rajtik T, Carnicka S, Ravingerova T, Adameova A. Mitigation of postischemic cardiac contractile dysfunction by CaMKII inhibition: Effects on programmed necrotic and apoptotic cell death. Mol Cell Biochem 2014;388:269-276.
249. Joshi SR, Dhagia V, Gairhe S, Edwards JG, McMurtry IF, Gupte SA. MicroRNA-140 is elevated and mitofusin-1 is downregulated in the right ventricle of the Sugen5416/hypoxia/normoxia model of pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol 2016;311:H689-H698.
250. Watts JA, Gellar MA, Stuart LK, Obraztsova M, Kline JA. Proinflammatory events in right ventricular damage during pulmonary embolism: Effects of treatment with ketorolac in rats. J Cardiovasc Pharmacol 2009;54:246-252.
251. Lavine KJ, Epelman S, Uchida K, Weber KJ, Nichols CG, Schilling JD, et al. Distinct macrophage lineages contribute to disparate patterns of cardiac recovery and remodeling in the neonatal and adult heart. Proc Natl Acad Sci USA 2014;111:16029-16034. [Published erratum appears in Proc Natl Acad Sci USA 113:E1414.]
252. Rain S, Andersen S, Najafi A, Gammelgaard Schultz J, da Silva Gonçalves Bós D, Handoko ML, et al. Right ventricular myocardial stiffness in experimental pulmonary arterial hypertension: Relative contribution of fibrosis and myofibril stiffness. Circ Heart Fail 2016; 9:e002636.
253. Hadri L, Kratlian RG, Benard L, Maron BA, Dorfmüller P, Ladage D, et al. Therapeutic efficacy of AAV1.SERCA2a in monocrotaline-induced pulmonary arterial hypertension. Circulation 2013;128:512-523.
254. Hsu S, Kokkonen-Simon KM, Kirk JA, Kolb TM, Damico RL, Mathai SC, et al. Right ventricular myofilament functional differences in humans with systemic sclerosis-associated versus idiopathic pulmonary arterial hypertension. Circulation 2018;137: 2360-2370.
255. Folino A, Montarolo PG, Samaja M, Rastaldo R. Effects of apelin on the cardiovascular system. Heart Fail Rev 2015;20:505-518.
256. Dai T, Ramirez-Correa G, Gao WD. Apelin increases contractility in failing cardiac muscle. Eur J Pharmacol 2006;553:222-228.
257. Greenberg B, Butler J, Felker GM, Ponikowski P, Voors AA, Desai AS, et al. Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): A randomised, multinational, double-blind, placebo-controlled, phase 2b trial. Lancet 2016;387:1178-1186.
258. Hong Z, Chen KH, DasGupta A, Potus F, Dunham-Snary K, Bonnet S, et al. MicroRNA-138 and microRNA-25 down-regulate mitochondrial calcium uniporter, causing the pulmonary arterial hypertension cancer phenotype. Am J Respir Crit Care Med 2017; 195:515-529.
259. Provencher S, Herve P, Jais X, Lebrec D, Humbert M, Simonneau G, et al. Deleterious effects of beta-blockers on exercise capacity and hemodynamics in patients with portopulmonary hypertension. Gastroenterology 2006;130:120-126.
260. Grinnan D, Bogaard HJ, Grizzard J, Van Tassell B, Abbate A, DeWilde C, et al. Treatment of group I pulmonary arterial hypertension with carvedilol is safe. Am J Respir Crit Care Med 2014;189:1562-1564.
261. van Campen JS, de Boer K, van de Veerdonk MC, van der Bruggen CE, Allaart CP, Raijmakers PG, et al. Bisoprolol in idiopathic pulmonary arterial hypertension: An explorative study. Eur Respir J 2016;48:787-796.
262. Farha S, Saygin D, ParkMM, Cheong HI, Asosingh K, Comhair SA, et al. Pulmonary arterial hypertension treatment with carvedilol for heart failure: A randomized controlled trial. JCI Insight 2017;2:95240.
263. Perros F, de Man FS, Bogaard HJ, Antigny F, Simonneau G, Bonnet S, et al. Use of b-blockers in pulmonary hypertension. Circ Heart Fail 2017;10:e003703.
264. Werchan PM, Summer WR, Gerdes AM, McDonough KH. Right ventricular performance after monocrotaline-induced pulmonary hypertension. Am J Physiol 1989;256:H1328-H1336.
265. Hessel MH, Steendijk P, den Adel B, Schutte CI, van der Laarse A. Characterization of right ventricular function after monocrotalineinduced pulmonary hypertension in the intact rat. Am J Physiol Heart Circ Physiol 2006;291:H2424-H2430.
266. Schäfer S, Ellinghaus P, Janssen W, Kramer F, Lustig K, Milting H, et al. Chronic inhibition of phosphodiesterase 5 does not prevent pressure-overload-induced right-ventricular remodelling. Cardiovasc Res 2009;82:30-39.
267. Ostádal B, Urbanová D, Ressl J, Procházka J, Pelouch V, Widimský J. Changes of the right and left ventricles in rats exposed to intermittent high altitude hypoxia. Cor Vasa 1981;23:111-120.
268. Sharma S, Taegtmeyer H, Adrogue J, Razeghi P, Sen S, Ngumbela K, et al. Dynamic changes of gene expression in hypoxia-induced right ventricular hypertrophy. Am J Physiol Heart Circ Physiol 2004;286: H1185-H1192.
269. Gomez A, Mink S. Interaction between effects of hypoxia and hypercapnia on altering left ventricular relaxation and chamber stiffness in dogs. Am Rev Respir Dis 1992;146:313-320.
270. Dias CA, Assad RS, Caneo LF, Abduch MC, Aiello VD, Dias AR, et al. Reversible pulmonary trunk banding: II. An experimental model for rapid pulmonary ventricular hypertrophy. J Thorac Cardiovasc Surg 2002;124:999-1006.
271. Akhavein F, St-Michel EJ, Seifert E, Rohlicek CV. Decreased left ventricular function, myocarditis, and coronary arteriolar medial thickening following monocrotaline administration in adult rats. J Appl Physiol (1985) 2007;103:287-295.
272. Abe K, Toba M, Alzoubi A, Ito M, Fagan KA, Cool CD, et al. Formation of plexiform lesions in experimental severe pulmonary arterial hypertension. Circulation 2010;121:2747-2754.
273. Bogaard HJ, Natarajan R, Mizuno S, Abbate A, Chang PJ, Chau VQ, et al. Adrenergic receptor blockade reverses right heart remodeling and dysfunction in pulmonary hypertensive rats. Am J Respir Crit Care Med 2010;182:652-660.
274. Gomez-Arroyo JG, Farkas L, Alhussaini AA, Farkas D, Kraskauskas D, Voelkel NF, et al. The monocrotaline model of pulmonary hypertension in perspective. Am J Physiol Lung Cell Mol Physiol 2012;302:L363-L369.
275. Gomez-Arroyo J, Saleem SJ, Mizuno S, Syed AA, Bogaard HJ, Abbate A, et al. A brief overview of mouse models of pulmonary arterial hypertension: Problems and prospects. Am J Physiol Lung Cell Mol Physiol 2012;302:L977-L991.
276. Okada K, Tanaka Y, Bernstein M, Zhang W, Patterson GA, Botney MD. Pulmonary hemodynamics modify the rat pulmonary artery response to injury: A neointimal model of pulmonary hypertension. Am J Pathol 1997;151:1019-1025.
277. Gomez-Arroyo J, Mizuno S, Szczepanek K, Van Tassell B, Natarajan R, dos Remedios CG, et al. Metabolic gene remodeling and mitochondrial dysfunction in failing right ventricular hypertrophy secondary to pulmonary arterial hypertension. Circ Heart Fail 2013; 6:136-144.
278. Lahm T, Tuder RM, Petrache I. Progress in solving the sex hormone paradox in pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2014;307:L7-L26.
279. Brown MB, Chingombe TJ, Zinn AB, Reddy JG, Novack RA, Cooney SA, et al. Novel assessment of haemodynamic kinetics with acute exercise in a rat model of pulmonary arterial hypertension. Exp Physiol 2015;100:742-754.
280. Shiran H, Zamanian RT, McConnell MV, Liang DH, Dash R, Heidary S, et al. Relationship between echocardiographic and magnetic resonance derived measures of right ventricular size and function in patients with pulmonary hypertension. J Am Soc Echocardiogr 2014;27:405-412.
281. Sato T, Tsujino I, Ohira H, Oyama-Manabe N, Yamada A, Ito YM, et al. Validation study on the accuracy of echocardiographic measurements of right ventricular systolic function in pulmonary hypertension. J Am Soc Echocardiogr 2012;25:280-286.
282. Grapsa J, Pereira Nunes MC, Tan TC, Cabrita IZ, Coulter T, Smith BC, et al. Echocardiographic and hemodynamic predictors of survival in precapillary pulmonary hypertension: Seven-year follow-up. Circ Cardiovasc Imaging 2015;8:e002107.
283. Badagliacca R, Reali M, Poscia R, Pezzuto B, Papa S, Mezzapesa M, et al. Right intraventricular dyssynchrony in idiopathic, heritable, and anorexigen-induced pulmonary arterial hypertension: Clinical impact and reversibility. JACC Cardiovasc Imaging 2015;8:642-652.
284. Mauritz GJ, Kind T, Marcus JT, Bogaard HJ, van de Veerdonk M, Postmus PE, et al. Progressive changes in right ventricular geometric shortening and long-term survival in pulmonary arterial hypertension. Chest 2012;141:935-943.
285. Spruijt OA, Di Pasqua MC, Bogaard HJ, van der Bruggen CE, Oosterveer F, Marcus JT, et al. Serial assessment of right ventricular systolic function in patients with precapillary pulmonary hypertension using simple echocardiographic parameters: A comparison with cardiac magnetic resonance imaging. J Cardiol 2017;69:182-188.
286. Kind T, Mauritz GJ, Marcus JT, van de Veerdonk M, Westerhof N, Vonk-Noordegraaf A. Right ventricular ejection fraction is better reflected by transverse rather than longitudinal wall motion in pulmonary hypertension. J Cardiovasc Magn Reson 2010;12:35.
287. Okumura K, Humpl T, Dragulescu A, Mertens L, Friedberg MK. Longitudinal assessment of right ventricular myocardial strain in relation to transplant-free survival in children with idiopathic pulmonary hypertension. J Am Soc Echocardiogr 2014;27:1344-1351.
288. Mukherjee M, Mercurio V, Tedford RJ, Shah AA, Hsu S, Mullin CJ, et al. Right ventricular longitudinal strain is diminished in systemic sclerosis compared with idiopathic pulmonary arterial hypertension. Eur Respir J 2017;50:1701436.
289. Bradlow WM, Hughes ML, Keenan NG, Bucciarelli-Ducci C, Assomull R, Gibbs JS, et al. Measuring the heart in pulmonary arterial hypertension (PAH): Implications for trial study size. J Magn Reson Imaging 2010;31:117-124.
290. Grapsa J, O'Regan DP, Pavlopoulos H, Durighel G, Dawson D, Nihoyannopoulos P. Right ventricular remodelling in pulmonary arterial hypertension with three-dimensional echocardiography: Comparison with cardiac magnetic resonance imaging. Eur J Echocardiogr 2010;11:64-73.
291. Niemann PS, Pinho L, Balbach T, Galuschky C, Blankenhagen M, Silberbach M, et al. Anatomically oriented right ventricular volume measurements with dynamic three-dimensional echocardiography validated by 3-Tesla magnetic resonance imaging. J Am Coll Cardiol 2007;50:1668-1676.
292. Ostenfeld E, Carlsson M, Shahgaldi K, Roijer A, Holm J. Manual correction of semi-automatic three-dimensional echocardiography is needed for right ventricular assessment in adults; validation with cardiac magnetic resonance. Cardiovasc Ultrasound 2012;10:1.
293. Shimada YJ, Shiota M, Siegel RJ, Shiota T. Accuracy of right ventricular volumes and function determined by three-dimensional echocardiography in comparison with magnetic resonance imaging: A meta-analysis study. J Am Soc Echocardiogr 2010;23: 943-953.
294. van der Zwaan HB, Geleijnse ML, McGhie JS, Boersma E, Helbing WA, Meijboom FJ, et al. Right ventricular quantification in clinical practice: Two-dimensional vs. three-dimensional echocardiography compared with cardiac magnetic resonance imaging. Eur J Echocardiogr 2011;12:656-664.
295. van de Veerdonk MC, Marcus JT, Westerhof N, de Man FS, Boonstra A, Heymans MW, et al. Signs of right ventricular deterioration in clinically stable patients with pulmonary arterial hypertension. Chest 2015;147:1063-1071.
296. McCann GP, Gan CT, Beek AM, Niessen HW, Vonk Noordegraaf A, van Rossum AC. Extent of MRI delayed enhancement of myocardial mass is related to right ventricular dysfunction in pulmonary artery hypertension. AJR Am J Roentgenol 2007;188:349-355.
297. Reiter U, Reiter G, Kovacs G, Adelsmayr G, Greiser A, Olschewski H, et al. Native myocardial T1 mapping in pulmonary hypertension: Correlations with cardiac function and hemodynamics. Eur Radiol 2017;27:157-166.
298. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, et al.; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:e147-e239.
299. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: Executive summary: A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013;128:1810-1852.
300. Surie S, Bouma BJ, Bruin-Bon RA, Hardziyenka M, Kloek JJ, Van der Plas MN, et al. Time course of restoration of systolic and diastolic right ventricular function after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Am Heart J 2011;161:1046-1052.
301. Katz WE, Gasior TA, Quinlan JJ, Lazar JM, Firestone L, Griffith BP, et al. Immediate effects of lung transplantation on right ventricular morphology and function in patients with variable degrees of pulmonary hypertension. J Am Coll Cardiol 1996;27:384-391.
302. Austin ED, Kawut SM, Gladwin MT, Abman SH. Pulmonary hypertension: NHLBI workshop on the primary prevention of chronic lung diseases. Ann Am Thorac Soc 2014;11:S178-S185.