Skip to main content
SpringerLink
Log in

Pulmonary Vascular Disease: Hemodynamic Assessment and Treatment Selection—Focus on Group II Pulmonary Hypertension

  • Pharmacologic Therapy (W.H.W. Tang, Section Editor)
  • Published:
Current Heart Failure Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Pulmonary hypertension due to left heart disease (PH-LHD) is the most common cause of pulmonary hypertension worldwide, yet therapies used to treat pulmonary arterial hypertension have failed to show efficacy in this population. Proper hemodynamic assessment and differentiation of pulmonary hypertension phenotypes is therefore critical for both current clinical practice and future research and therapeutic efforts.

Recent Findings

Substantial recent efforts have sought to improve the hemodynamic characterization of pulmonary hypertension for both diagnostic and prognostic purposes. These efforts include identifying occult LHD using provocative maneuvers as well as sub-classifying PH-LHD based on the presence or absence of a pre-capillary component. How to best define the pre-capillary component remains controversial as several studies have drawn conflicting conclusions. The lack of standardization of hemodynamic measurements as well as measurement fidelity concerns may explain some of the discrepant results. Non-hemodynamic methods of PH-LHD classification may also have an emerging role. Despite recent advances, therapeutic studies have largely remained disappointing.

Summary

In this review, we discuss the nuances and controversies surrounding diagnostic and prognostic hemodynamic characterization of PH-LHD as well as summarize the recent therapeutic efforts and ongoing challenges in this population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Vachiery JL, et al. Pulmonary hypertension due to left heart diseases. J Am Coll Cardiol. 2013;62(25 Suppl):D100–8. https://doi.org/10.1016/j.jacc.2013.10.033.

    Article  PubMed  Google Scholar 

  2. Fang JC, DeMarco T, Givertz MM, Borlaug BA, Lewis GD, Rame JE, et al. World Health Organization Pulmonary Hypertension Group 2: pulmonary hypertension due to left heart disease in the adult—a summary statement from the Pulmonary Hypertension Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2012;31(9):913–33. https://doi.org/10.1016/j.healun.2012.06.002.

    Article  PubMed  Google Scholar 

  3. Guazzi M, Borlaug BA. Pulmonary hypertension due to left heart disease. Circulation. 2012;126(8):975–90. https://doi.org/10.1161/CIRCULATIONAHA.111.085761.

    Article  PubMed  Google Scholar 

  4. Galie N, 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): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67–119. https://doi.org/10.1093/eurheartj/ehv317.

    Article  PubMed  Google Scholar 

  5. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D34–41. https://doi.org/10.1016/j.jacc.2013.10.029.

    Article  PubMed  Google Scholar 

  6. Delgado JF, Conde E, Sánchez V, López-Ríos F, Gómez-Sánchez MA, Escribano P, et al. Pulmonary vascular remodeling in pulmonary hypertension due to chronic heart failure. Eur J Heart Fail. 2005;7(6):1011–6. https://doi.org/10.1016/j.ejheart.2004.10.021.

    Article  PubMed  Google Scholar 

  7. • Gerges C, et al. Diastolic pulmonary vascular pressure gradient: a predictor of prognosis in "out-of-proportion" pulmonary hypertension. Chest. 2013;143(3):758–66. This study found that in patients with postcapillary PH and TPG >12mmHg, DPG > 7mmHg was associated with a worse median survival. In 18 patients, lung tissue in patients with elevated DPG was evaluated and showed advanced remodeling of the vasculature.

    Article  PubMed  Google Scholar 

  8. Tedford RJ, Beaty CA, Mathai SC, Kolb TM, Damico R, Hassoun PM, et al. Prognostic value of the pre-transplant diastolic pulmonary artery pressure-to-pulmonary capillary wedge pressure gradient in cardiac transplant recipients with pulmonary hypertension. J Heart Lung Transplant. 2014;33(3):289–97. https://doi.org/10.1016/j.healun.2013.11.008.

    Article  PubMed  Google Scholar 

  9. • Tampakakis E, et al. The diastolic pulmonary gradient does not predict survival in patients with pulmonary hypertension due to left heart disease. JACC Heart Fail. 2015;3(1):9–16. In this retrospective, largely HFrEF cohort, DPG was not associated with mortality in PH-LHD. TPG and PVR both predicted mortality. 36% of PH-LHD patients had a negative DPG.

    Article  PubMed  Google Scholar 

  10. • Al-Naamani N, et al. Pulmonary arterial capacitance is an important predictor of mortality in heart failure with a preserved ejection fraction. JACC Heart Fail. 2015;3(6):467–74. This study found that pulmonary vascular compliance was the best predictor of mortality in a PH-HFpEF cohort. DPG did not predict outcome, and acute vasodilator response was not associated with improved survival (inhaled NO).

    Article  PubMed  PubMed Central  Google Scholar 

  11. • Assad TR, et al. Clinical and biological insights into combined post- and pre-capillary pulmonary hypertension. J Am Coll Cardiol. 2016;68(23):2525–36. Patients with CpcPH had genetic polymorphisms shared with PAH that were not present in Ipc-PH patients in this novel study.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Nagy AI, Venkateshvaran A, Merkely B, Lund LH, Manouras A. Determinants and prognostic implications of the negative diastolic pulmonary pressure gradient in patients with pulmonary hypertension due to left heart disease. Eur J Heart Fail. 2017;19(1):88–97. https://doi.org/10.1002/ejhf.675.

    Article  CAS  PubMed  Google Scholar 

  13. • Palazzini, M., et al., Pulmonary hypertension due to left heart disease: analysis of survival according to the haemodynamic classification of the 2015 ESC/ERS guidelines and insights for future changes. Eur J Heart Fail, 2017. In PH-LHD patients, using the revised ESC/ERS guidelines, no difference in survival was noted between CpcPH and Ipc-PH. PVR had a better predictive value than DPG in PH-LHD patients.

  14. Adir Y, Guazzi M, Offer A, Temporelli PL, Cannito A, Ghio S. Pulmonary hemodynamics in heart failure patients with reduced or preserved ejection fraction and pulmonary hypertension: similarities and disparities. Am Heart J. 2017;192:120–7. https://doi.org/10.1016/j.ahj.2017.06.006.

    Article  PubMed  Google Scholar 

  15. • Wright SP, et al. Diastolic pressure difference to classify pulmonary hypertension in the assessment of heart transplant candidates. Circ Heart Fail, 2017. 10(9). This study employed QRS-gating methods to assess the PAWP, which led to overall higher DPG values, a greater proportion of CpcPH patients, and fewer negative DPG values compared to usual methods.

  16. Ghio, S., Crimi G., Temporelli P.L., Traversi E., la Rovere M.T., Cannito A., Vizza D., Scelsi L., Raineri C., Guazzi M., Oltrona Visconti L., Haemodynamic effects of an acute vasodilator challenge in heart failure patients with reduced ejection fraction and different forms of post-capillary pulmonary hypertension. Eur J Heart Fail, 2017. https://doi.org/10.1002/ejhf.1067.

  17. Caravita S, Faini A, Deboeck G, Bondue A, Naeije R, Parati G, et al. Pulmonary hypertension and ventilation during exercise: role of the pre-capillary component. J Heart Lung Transplant. 2017;36(7):754–62. https://doi.org/10.1016/j.healun.2016.12.011.

    Article  PubMed  Google Scholar 

  18. Tedford RJ, Hassoun PM, Mathai SC, Girgis RE, Russell SD, Thiemann DR, et al. Pulmonary capillary wedge pressure augments right ventricular pulsatile loading. Circulation. 2012;125(2):289–97. https://doi.org/10.1161/CIRCULATIONAHA.111.051540.

    Article  PubMed  Google Scholar 

  19. Naeije R, Vachiery JL, Yerly P, Vanderpool R. The transpulmonary pressure gradient for the diagnosis of pulmonary vascular disease. Eur Respir J. 2013;41(1):217–23. https://doi.org/10.1183/09031936.00074312.

    Article  PubMed  Google Scholar 

  20. Gerges M, Gerges C, Pistritto AM, Lang MB, Trip P, Jakowitsch J, et al. Pulmonary hypertension in heart failure. Epidemiology, right ventricular function, and survival. Am J Respir Crit Care Med. 2015;192(10):1234–46. https://doi.org/10.1164/rccm.201503-0529OC.

    Article  PubMed  Google Scholar 

  21. Mazimba S, Kennedy JLW, Zhuo D, Bergin J, Abuannadi M, Tallaj J, et al. Decreased pulmonary arterial proportional pulse pressure after pulmonary artery catheter optimization for advanced heart failure is associated with adverse clinical outcomes. J Card Fail. 2016;22(12):954–61. https://doi.org/10.1016/j.cardfail.2016.03.019.

    Article  PubMed  Google Scholar 

  22. Enson Y, Wood JA, Mantaras NB, Harvey RM. The influence of heart rate on pulmonary arterial-left ventricular pressure relationships at end-diastole. Circulation. 1977;56(4 Pt 1):533–9. https://doi.org/10.1161/01.CIR.56.4.533.

    Article  CAS  PubMed  Google Scholar 

  23. Guazzi M, Naeije R. Pulmonary hypertension in heart failure: Pathophysiology, Pathobiology, and Emerging Clinical Perspectives. J Am Coll Cardiol. 2017;69(13):1718–34. https://doi.org/10.1016/j.jacc.2017.01.051.

    Article  PubMed  Google Scholar 

  24. Naeije R. Measurement to predict survival: the case of diastolic pulmonary gradient. JACC Heart Fail. 2015;3(5):425. https://doi.org/10.1016/j.jchf.2014.12.014.

    Article  PubMed  Google Scholar 

  25. Gerges M, Gerges C, Lang IM. How to define pulmonary hypertension due to left heart disease. Eur Respir J. 2016;48(2):553–5. https://doi.org/10.1183/13993003.00432-2016.

    Article  PubMed  Google Scholar 

  26. Lankhaar JW, Westerhof N, Faes TJC, Tji-Joong Gan C, Marques KM, Boonstra A, et al. Pulmonary vascular resistance and compliance stay inversely related during treatment of pulmonary hypertension. Eur Heart J. 2008;29(13):1688–95. https://doi.org/10.1093/eurheartj/ehn103.

    Article  PubMed  Google Scholar 

  27. Dupont M, Mullens W, Skouri HN, Abrahams Z, Wu Y, Taylor DO, et al. Prognostic role of pulmonary arterial capacitance in advanced heart failure. Circ Heart Fail. 2012;5(6):778–85. https://doi.org/10.1161/CIRCHEARTFAILURE.112.968511.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Pellegrini P, Rossi A, Pasotti M, Raineri C, Cicoira M, Bonapace S, et al. Prognostic relevance of pulmonary arterial compliance in patients with chronic heart failure. Chest. 2014;145(5):1064–70. https://doi.org/10.1378/chest.13-1510.

    Article  PubMed  Google Scholar 

  29. Kovacs G, Avian A, Olschewski A, Olschewski H. Zero reference level for right heart catheterisation. Eur Respir J. 2013;42(6):1586–94. https://doi.org/10.1183/09031936.00050713.

    Article  PubMed  Google Scholar 

  30. Hoeper MM, Bogaard HJ, Condliffe R, Frantz R, Khanna D, Kurzyna M, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D42–50. https://doi.org/10.1016/j.jacc.2013.10.032.

    Article  PubMed  Google Scholar 

  31. Kovacs G, Herve P, Barbera JA, Chaouat A, Chemla D, Condliffe R, et al. An official European Respiratory Society statement: pulmonary haemodynamics during exercise. Eur Respir J. 2017;50(5):1700578. https://doi.org/10.1183/13993003.00578-2017.

    Article  PubMed  Google Scholar 

  32. Scruggs V, Pietras RJ, Rosen KM. Frequency response of fluid-filled catheter-micromanometer systems used for measurement of left ventricular pressure. Am Heart J. 1975;89(5):619–24. https://doi.org/10.1016/0002-8703(75)90508-6.

    Article  CAS  PubMed  Google Scholar 

  33. Brower RW, Spaans W, Rewiersma PA, Meester GT. A fully automatic device for compensating for artifacts in conventional catheter-manometer pressure recordings. Biomed Eng. 1975;10(8):305–10.

    CAS  PubMed  Google Scholar 

  34. Lim, M., et al., Hemodynamic rounds: interpretation of cardiac pathophysiology from pressure waveform analysis, 3rd edition, ed. M. Kern. 2009: John Wiley & Sons, Inc.

  35. Dickinson MG, Lam CS, Rienstra M, Vonck TE, Hummel YM, Voors AA, et al. Atrial fibrillation modifies the association between pulmonary artery wedge pressure and left ventricular end-diastolic pressure. Eur J Heart Fail. 2017;19(11):1483–90. https://doi.org/10.1002/ejhf.959.

    Article  PubMed  Google Scholar 

  36. Tampakakis E, Tedford RJ. Balancing the positives and negatives of the diastolic pulmonary gradient. Eur J Heart Fail. 2017;19(1):98–100. https://doi.org/10.1002/ejhf.704.

    Article  PubMed  Google Scholar 

  37. Houston BA, Tedford RJ. Is pulmonary artery wedge pressure a Fib in A-Fib? Eur J Heart Fail. 2017;19(11):1491–4. https://doi.org/10.1002/ejhf.992.

    Article  PubMed  Google Scholar 

  38. Houston BA, Tedford RJ. What we talk about when we talk about the wedge pressure. Circ Heart Fail. 2017;10(9):e004450. https://doi.org/10.1161/CIRCHEARTFAILURE.117.004450.

    Article  PubMed  Google Scholar 

  39. Halpern SD, Taichman DB. Misclassification of pulmonary hypertension due to reliance on pulmonary capillary wedge pressure rather than left ventricular end-diastolic pressure. Chest. 2009;136(1):37–43. https://doi.org/10.1378/chest.08-2784.

    Article  PubMed  Google Scholar 

  40. Braunwald E, Frahm CJ, Ross J Jr. Studies on Starling's law of the heart. V. Left ventricular function in man. J Clin Invest. 1961;40(10):1882–90. https://doi.org/10.1172/JCI104412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hoeper MM, et al. Determination of cardiac output by the Fick method, thermodilution, and acetylene rebreathing in pulmonary hypertension. Am J Respir Crit Care Med. 1999;160(2):535–41. https://doi.org/10.1164/ajrccm.160.2.9811062.

    Article  CAS  PubMed  Google Scholar 

  42. Ganz W, Donoso R, Marcus HS, Forrester JS, Swan HJC. A new technique for measurement of cardiac output by thermodilution in man. Am J Cardiol. 1971;27(4):392–6. https://doi.org/10.1016/0002-9149(71)90436-X.

    Article  CAS  PubMed  Google Scholar 

  43. Stevens JH, Raffin TA, Mihm FG, Rosenthal MH, Stetz CW. Thermodilution cardiac output measurement. Effects of the respiratory cycle on its reproducibility. JAMA. 1985;253(15):2240–2. https://doi.org/10.1001/jama.1985.03350390082030.

    Article  CAS  PubMed  Google Scholar 

  44. Nishikawa T, Dohi S. Errors in the measurement of cardiac output by thermodilution. Can J Anaesth. 1993;40(2):142–53. https://doi.org/10.1007/BF03011312.

    Article  CAS  PubMed  Google Scholar 

  45. Hillis LD, Firth BG, Winniford MD. Analysis of factors affecting the variability of Fick versus indicator dilution measurements of cardiac output. Am J Cardiol. 1985;56(12):764–8. https://doi.org/10.1016/0002-9149(85)91132-4.

    Article  CAS  PubMed  Google Scholar 

  46. Cigarroa RG, Lange RA, Williams RH, Bedotto JB, Hillis LD. Underestimation of cardiac output by thermodilution in patients with tricuspid regurgitation. Am J Med. 1989;86(4):417–20. https://doi.org/10.1016/0002-9343(89)90339-2.

    Article  CAS  PubMed  Google Scholar 

  47. Yung GL, Fedullo PF, Kinninger K, Johnson W, Channick RN. Comparison of impedance cardiography to direct Fick and thermodilution cardiac output determination in pulmonary arterial hypertension. Congest Heart Fail. 2004;10(2 Suppl 2):7–10. https://doi.org/10.1111/j.1527-5299.2004.03406.x.

    Article  PubMed  Google Scholar 

  48. Fakler U, Pauli C, Hennig M, Sebening W, Hess J. Assumed oxygen consumption frequently results in large errors in the determination of cardiac output. J Thorac Cardiovasc Surg. 2005;130(2):272–6. https://doi.org/10.1016/j.jtcvs.2005.02.048.

    Article  PubMed  Google Scholar 

  49. Narang N, Gore MO, Snell PG, Ayers CR, Lorenzo S, Carrick-Ranson G, et al. Accuracy of estimating resting oxygen uptake and implications for hemodynamic assessment. Am J Cardiol. 2012;109(4):594–8. https://doi.org/10.1016/j.amjcard.2011.10.010.

    Article  PubMed  Google Scholar 

  50. Narang N, Thibodeau JT, Levine BD, Gore MO, Ayers CR, Lange RA, et al. Inaccuracy of estimated resting oxygen uptake in the clinical setting. Circulation. 2014;129(2):203–10. https://doi.org/10.1161/CIRCULATIONAHA.113.003334.

    Article  CAS  PubMed  Google Scholar 

  51. Fares WH, Blanchard SK, Stouffer GA, Chang PP, Rosamond WD, Ford HJ, et al. Thermodilution and Fick cardiac outputs differ: impact on pulmonary hypertension evaluation. Can Respir J. 2012;19(4):261–6. https://doi.org/10.1155/2012/261793.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Opotowsky AR, Hess E, Maron BA, Brittain EL, Barón AE, Maddox TM, et al. Thermodilution vs estimated Fick cardiac output measurement in clinical practice: an analysis of mortality from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA CART) program and Vanderbilt University. JAMA Cardiol. 2017;2(10):1090–9. https://doi.org/10.1001/jamacardio.2017.2945.

    Article  PubMed  Google Scholar 

  53. Costard-Jackle A, Fowler MB. Influence of preoperative pulmonary artery pressure on mortality after heart transplantation: testing of potential reversibility of pulmonary hypertension with nitroprusside is useful in defining a high risk group. J Am Coll Cardiol. 1992;19(1):48–54. https://doi.org/10.1016/0735-1097(92)90050-W.

    Article  CAS  PubMed  Google Scholar 

  54. Mehra MR, et al. Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates—2006. J Heart Lung Transplant. 2006;25(9):1024–42. https://doi.org/10.1016/j.healun.2006.06.008.

    Article  PubMed  Google Scholar 

  55. Griepp RB, Stinson EB, Dong E, Clark DA, Shumway NE. Determinants of operative risk in human heart transplantation. Am J Surg. 1971;122(2):192–7. https://doi.org/10.1016/0002-9610(71)90316-3.

    Article  CAS  PubMed  Google Scholar 

  56. Murali S, Kormos RL, Uretsky BF, Schechter D, Reddy PS, Denys BG, et al. Preoperative pulmonary hemodynamics and early mortality after orthotopic cardiac transplantation: the Pittsburgh experience. Am Heart J. 1993;126(4):896–904. https://doi.org/10.1016/0002-8703(93)90704-D.

    Article  CAS  PubMed  Google Scholar 

  57. Kirklin JK, Naftel DC, Kirklin JW, Blackstone EH, White-Williams C, Bourge RC. Pulmonary vascular resistance and the risk of heart transplantation. J Heart Transplant. 1988;7(5):331–6.

    CAS  PubMed  Google Scholar 

  58. Givertz MM, Hare JM, Loh E, Gauthier DF, Colucci WS. Effect of bolus milrinone on hemodynamic variables and pulmonary vascular resistance in patients with severe left ventricular dysfunction: a rapid test for reversibility of pulmonary hypertension. J Am Coll Cardiol. 1996;28(7):1775–80. https://doi.org/10.1016/S0735-1097(96)00399-3.

    Article  CAS  PubMed  Google Scholar 

  59. von Scheidt W, et al. Prostaglandin E1 testing in heart failure-associated pulmonary hypertension enables transplantation: the PROPHET study. J Heart Lung Transplant. 2006;25(9):1070–6.

    Article  Google Scholar 

  60. Loh E, Stamler JS, Hare JM, Loscalzo J, Colucci WS. Cardiovascular effects of inhaled nitric oxide in patients with left ventricular dysfunction. Circulation. 1994;90(6):2780–5. https://doi.org/10.1161/01.CIR.90.6.2780.

    Article  CAS  PubMed  Google Scholar 

  61. Alaeddini J, Uber PA, Park MH, Scott RL, Ventura HO, Mehra MR. Efficacy and safety of sildenafil in the evaluation of pulmonary hypertension in severe heart failure. Am J Cardiol. 2004;94(11):1475–7. https://doi.org/10.1016/j.amjcard.2004.07.157.

    Article  CAS  PubMed  Google Scholar 

  62. Weston MW, Isaac BF, Crain C. The use of inhaled prostacyclin in nitroprusside-resistant pulmonary artery hypertension. J Heart Lung Transplant. 2001;20(12):1340–4. https://doi.org/10.1016/S1053-2498(01)00320-5.

    Article  CAS  PubMed  Google Scholar 

  63. Guglin M, Mehra S, Mason TJ. Comparison of drugs for pulmonary hypertension reversibility testing: a meta-analysis. Pulm Circ. 2013;3(2):406–13. https://doi.org/10.4103/2045-8932.113180.

    Article  PubMed  PubMed Central  Google Scholar 

  64. West JB, Dollery CT, Heard BE. Increased pulmonary vascular resistance in the dependent zone of the isolated dog lung caused by perivascular edema. Circ Res. 1965;17(3):191–206. https://doi.org/10.1161/01.RES.17.3.191.

    Article  PubMed  Google Scholar 

  65. Melenovsky V, Andersen MJ, Andress K, Reddy YN, Borlaug BA. Lung congestion in chronic heart failure: haemodynamic, clinical, and prognostic implications. Eur J Heart Fail. 2015;17(11):1161–71. https://doi.org/10.1002/ejhf.417.

    Article  CAS  PubMed  Google Scholar 

  66. Barnett CF, De Marco T. Pulmonary hypertension associated with left-sided heart disease. Heart Fail Clin. 2012;8(3):447–59. https://doi.org/10.1016/j.hfc.2012.04.009.

    Article  PubMed  Google Scholar 

  67. Al-Kindi SG, Farhoud M, Zacharias M, Ginwalla MB, ElAmm CA, Benatti RD, et al. Left ventricular assist devices or inotropes for decreasing pulmonary vascular resistance in patients with pulmonary hypertension listed for heart transplantation. J Card Fail. 2017;23(3):209–15. https://doi.org/10.1016/j.cardfail.2016.06.421.

    Article  PubMed  Google Scholar 

  68. Mikus E, Stepanenko A, Krabatsch T, Loforte A, Dandel M, Lehmkuhl HB, et al. Reversibility of fixed pulmonary hypertension in left ventricular assist device support recipients. Eur J Cardiothorac Surg. 2011;40(4):971–7. https://doi.org/10.1016/j.ejcts.2011.01.019.

    PubMed  Google Scholar 

  69. Alba AC, Rao V, Ross HJ, Jensen AS, Sander K, Gustafsson F, et al. Impact of fixed pulmonary hypertension on postheart transplant outcomes in bridge-to-transplant patients. J Heart Lung Transplant. 2010;29(11):1253–8. https://doi.org/10.1016/j.healun.2010.06.002.

    Article  PubMed  Google Scholar 

  70. Masri SC, Tedford RJ, Colvin MM, Leary PJ, Cogswell R. Pulmonary arterial compliance improves rapidly after left ventricular assist device implantation. ASAIO J. 2017;63(2):139–43. https://doi.org/10.1097/MAT.0000000000000467.

    Article  PubMed  Google Scholar 

  71. Borlaug BA, Nishimura RA, Sorajja P, Lam CSP, Redfield MM. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ Heart Fail. 2010;3(5):588–95. https://doi.org/10.1161/CIRCHEARTFAILURE.109.930701.

    Article  PubMed  PubMed Central  Google Scholar 

  72. • D'Alto M, et al. Clinical relevance of fluid challenge in patients evaluated for pulmonary hypertension. Chest. 2017;151(1):119–26. Using a cutoff of 18mmHg for the PAWP, fluid challenge with 7 mL/kg of saline allowed reclassication of 6–8% of patients from precapillary PH or normal to PH-LHD.

    Article  PubMed  Google Scholar 

  73. Robbins IM, Hemnes AR, Pugh ME, Brittain EL, Zhao DX, Piana RN, et al. High prevalence of occult pulmonary venous hypertension revealed by fluid challenge in pulmonary hypertension. Circ Heart Fail. 2014;7(1):116–22. https://doi.org/10.1161/CIRCHEARTFAILURE.113.000468.

    Article  PubMed  Google Scholar 

  74. • Hsu S, et al. Use of thermodilution cardiac output overestimates diagnoses of exercise-induced pulmonary hypertension. Pulm Circ. 2017;7(1):253–5. In this study, thermodilution underestimated cardiac output during exercise compared with direct Fick.

    Article  PubMed  PubMed Central  Google Scholar 

  75. • Wright SP, et al. The pulmonary artery wedge pressure response to sustained exercise is time-variant in healthy adults. Heart. 2016;102(6):438–43. This study described the pulmonary pressure response to sustained, submaximal exercise in healthy volunteers, finding that PAWP may routinely increase to >20mmHg early in exercise, and that PAWP and PA pressures may decline during continued exercise.

    Article  PubMed  Google Scholar 

  76. Wolsk E, Bakkestrøm R, Thomsen JH, Balling L, Andersen MJ, Dahl JS, et al. The influence of age on hemodynamic parameters during rest and exercise in healthy individuals. JACC Heart Fail. 2017;5(5):337–46. https://doi.org/10.1016/j.jchf.2016.10.012.

    Article  PubMed  Google Scholar 

  77. Thenappan T, Shah SJ, Gomberg-Maitland M, Collander B, Vallakati A, Shroff P, et al. Clinical characteristics of pulmonary hypertension in patients with heart failure and preserved ejection fraction. Circ Heart Fail. 2011;4(3):257–65. https://doi.org/10.1161/CIRCHEARTFAILURE.110.958801.

    Article  PubMed  Google Scholar 

  78. Tolle JJ, Waxman AB, van Horn TL, Pappagianopoulos PP, Systrom DM. Exercise-induced pulmonary arterial hypertension. Circulation. 2008;118(21):2183–9. https://doi.org/10.1161/CIRCULATIONAHA.108.787101.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Mullin CJ, Hsu S, Amancherla K, Wand A, Rhodes P, Leary PJ, et al. Evaluation of criteria for exercise-induced pulmonary hypertension in patients with resting pulmonary hypertension. Eur Respir J. 2017;50(3):1700784. https://doi.org/10.1183/13993003.00784-2017.

    Article  PubMed  Google Scholar 

  80. Oldham WM, Lewis GD, Opotowsky AR, Waxman AB, Systrom DM. Unexplained exertional dyspnea caused by low ventricular filling pressures: results from clinical invasive cardiopulmonary exercise testing. Pulm Circ. 2016;6(1):55–62. https://doi.org/10.1086/685054.

    Article  PubMed  PubMed Central  Google Scholar 

  81. 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(24):2413–22. https://doi.org/10.1161/CIRCULATIONAHA.116.022082.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Fujimoto N, Borlaug BA, Lewis GD, Hastings JL, Shafer KM, Bhella PS, et al. Hemodynamic responses to rapid saline loading: the impact of age, sex, and heart failure. Circulation. 2013;127(1):55–62. https://doi.org/10.1161/CIRCULATIONAHA.112.111302.

    Article  CAS  PubMed  Google Scholar 

  83. Borlaug BA. Invasive assessment of pulmonary hypertension: time for a more fluid approach? Circ Heart Fail. 2014;7(1):2–4. https://doi.org/10.1161/CIRCHEARTFAILURE.113.000983.

    Article  PubMed  Google Scholar 

  84. Andersen MJ, Olson TP, Melenovsky V, Kane GC, Borlaug BA. Differential hemodynamic effects of exercise and volume expansion in people with and without heart failure. Circ Heart Fail. 2015;8(1):41–8. https://doi.org/10.1161/CIRCHEARTFAILURE.114.001731.

    Article  PubMed  Google Scholar 

  85. Naeije R, D'Alto M. The diagnostic challenge of group 2 pulmonary hypertension. Prog Cardiovasc Dis. 2016;59(1):22–9. https://doi.org/10.1016/j.pcad.2016.05.003.

    Article  PubMed  Google Scholar 

  86. Tyberg JV, Taichman GC, Smith ER, Douglas NW, Smiseth OA, Keon WJ. The relationship between pericardial pressure and right atrial pressure: an intraoperative study. Circulation. 1986;73(3):428–32. https://doi.org/10.1161/01.CIR.73.3.428.

    Article  CAS  PubMed  Google Scholar 

  87. Kovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J. 2009;34(4):888–94. https://doi.org/10.1183/09031936.00145608.

    Article  CAS  PubMed  Google Scholar 

  88. Maeder MT, Thompson BR, Brunner-la Rocca HP, Kaye DM. Hemodynamic basis of exercise limitation in patients with heart failure and normal ejection fraction. J Am Coll Cardiol. 2010;56(11):855–63. https://doi.org/10.1016/j.jacc.2010.04.040.

    Article  PubMed  Google Scholar 

  89. Lewis GD, Murphy RM, Shah RV, Pappagianopoulos PP, Malhotra R, Bloch KD, et al. Pulmonary vascular response patterns during exercise in left ventricular systolic dysfunction predict exercise capacity and outcomes. Circ Heart Fail. 2011;4(3):276–85. https://doi.org/10.1161/CIRCHEARTFAILURE.110.959437.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Boerrigter BG, Waxman AB, Westerhof N, Vonk-Noordegraaf A, Systrom DM. Measuring central pulmonary pressures during exercise in COPD: how to cope with respiratory effects. Eur Respir J. 2014;43(5):1316–25. https://doi.org/10.1183/09031936.00016913.

    Article  PubMed  Google Scholar 

  91. Lewis GD, Bossone E, Naeije R, Grunig E, Saggar R, Lancellotti P, et al. Pulmonary vascular hemodynamic response to exercise in cardiopulmonary diseases. Circulation. 2013;128(13):1470–9. https://doi.org/10.1161/CIRCULATIONAHA.112.000667.

    Article  PubMed  Google Scholar 

  92. Bevegard S, Holmgren A, Jonsson B. Circulatory studies in well trained athletes at rest and during heavy exercise. With special reference to stroke volume and the influence of body position. Acta Physiol Scand. 1963;57(1-2):26–50. https://doi.org/10.1111/j.1748-1716.1963.tb02572.x.

    Article  CAS  PubMed  Google Scholar 

  93. Thadani U, Parker JO. Hemodynamics at rest and during supine and sitting bicycle exercise in normal subjects. Am J Cardiol. 1978;41(1):52–9. https://doi.org/10.1016/0002-9149(78)90131-5.

    Article  CAS  PubMed  Google Scholar 

  94. Oliveira RK, et al. Age-related upper limits of normal for maximum upright exercise pulmonary haemodynamics. Eur Respir J. 2016;47(4):1179–88. https://doi.org/10.1183/13993003.01307-2015.

    Article  PubMed  Google Scholar 

  95. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, 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(16):1810–52. https://doi.org/10.1161/CIR.0b013e31829e8807.

    Article  PubMed  Google Scholar 

  96. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey d Jr, Colvin MM, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137–61. https://doi.org/10.1161/CIR.0000000000000509.

    Article  PubMed  Google Scholar 

  97. Binanay C, Califf RM, Hasselblad V, O'Connor CM, Shah MR, Sopko G, et al. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial. JAMA. 2005;294(13):1625–33. https://doi.org/10.1001/jama.294.13.1625.

    Article  PubMed  Google Scholar 

  98. Abraham WT, Adamson PB, Bourge RC, Aaron MF, Costanzo MR, Stevenson LW, et al. Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial. Lancet. 2011;377(9766):658–66. https://doi.org/10.1016/S0140-6736(11)60101-3.

    Article  PubMed  Google Scholar 

  99. Haddad H, Elabbassi W, Moustafa S, Davies R, Mesana T, Hendry P, et al. Left ventricular assist devices as bridge to heart transplantation in congestive heart failure with pulmonary hypertension. ASAIO J. 2005;51(4):456–60. https://doi.org/10.1097/01.mat.0000169125.21268.d7.

    Article  PubMed  Google Scholar 

  100. Zimpfer D, Zrunek P, Roethy W, Czerny M, Schima H, Huber L, et al. Left ventricular assist devices decrease fixed pulmonary hypertension in cardiac transplant candidates. J Thorac Cardiovasc Surg. 2007;133(3):689–95. https://doi.org/10.1016/j.jtcvs.2006.08.104.

    Article  PubMed  Google Scholar 

  101. Givertz MM, Colucci WS, LeJemtel TH, Gottlieb SS, Hare JM, Slawsky MT, et al. Acute endothelin A receptor blockade causes selective pulmonary vasodilation in patients with chronic heart failure. Circulation. 2000;101(25):2922–7. https://doi.org/10.1161/01.CIR.101.25.2922.

    Article  CAS  PubMed  Google Scholar 

  102. Spieker LE, Mitrovic V, Noll G, Pacher R, Schulze MR, Muntwyler J, et al. Acute hemodynamic and neurohumoral effects of selective ET(A) receptor blockade in patients with congestive heart failure. ET 003 investigators. J Am Coll Cardiol. 2000;35(7):1745–52. https://doi.org/10.1016/S0735-1097(00)00649-5.

    Article  CAS  PubMed  Google Scholar 

  103. Porter TR, Taylor DO, Cycan A, Fields J, Bagley CW, Pandian NG, et al. Endothelium-dependent pulmonary artery responses in chronic heart failure: influence of pulmonary hypertension. J Am Coll Cardiol. 1993;22(5):1418–24. https://doi.org/10.1016/0735-1097(93)90552-C.

    Article  CAS  PubMed  Google Scholar 

  104. Califf RM, Adams KF, McKenna WJ, Gheorghiade M, Uretsky BF, McNulty SE, et al. A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: the Flolan International Randomized Survival Trial (FIRST). Am Heart J. 1997;134(1):44–54. https://doi.org/10.1016/S0002-8703(97)70105-4.

    Article  CAS  PubMed  Google Scholar 

  105. Packer M, McMurray J, Massie BM, Caspi A, Charlon V, Cohen-Solal A, et al. Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot study. J Card Fail. 2005;11(1):12–20. https://doi.org/10.1016/j.cardfail.2004.05.006.

    Article  CAS  PubMed  Google Scholar 

  106. Luscher TF, et al. Hemodynamic and neurohumoral effects of selective endothelin A (ET(A)) receptor blockade in chronic heart failure: the Heart Failure ET(A) Receptor Blockade Trial (HEAT). Circulation. 2002;106(21):2666–72. https://doi.org/10.1161/01.CIR.0000038497.80095.E1.

    Article  PubMed  CAS  Google Scholar 

  107. Anand I, McMurray J, Cohn JN, Konstam MA, Notter T, Quitzau K, et al. Long-term effects of darusentan on left-ventricular remodelling and clinical outcomes in the EndothelinA Receptor Antagonist Trial in Heart Failure (EARTH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364(9431):347–54. https://doi.org/10.1016/S0140-6736(04)16723-8.

    Article  CAS  PubMed  Google Scholar 

  108. McMurray JJ, et al. Effects of tezosentan on symptoms and clinical outcomes in patients with acute heart failure: the VERITAS randomized controlled trials. JAMA. 2007;298(17):2009–19. https://doi.org/10.1001/jama.298.17.2009.

    Article  CAS  PubMed  Google Scholar 

  109. Humbert M, et al. Pulmonary edema complicating continuous intravenous prostacyclin in pulmonary capillary hemangiomatosis. Am J Respir Crit Care Med. 1998;157(5 Pt 1):1681–5. https://doi.org/10.1164/ajrccm.157.5.9708065.

    Article  CAS  PubMed  Google Scholar 

  110. Preston IR, Klinger JR, Houtchens J, Nelson D, Mehta S, Hill NS. Pulmonary edema caused by inhaled nitric oxide therapy in two patients with pulmonary hypertension associated with the CREST syndrome. Chest. 2002;121(2):656–9. https://doi.org/10.1378/chest.121.2.656.

    Article  PubMed  Google Scholar 

  111. Katz SD, Balidemaj K, Homma S, Wu H, Wang J, Maybaum S. Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure. J Am Coll Cardiol. 2000;36(3):845–51. https://doi.org/10.1016/S0735-1097(00)00790-7.

    Article  CAS  PubMed  Google Scholar 

  112. Jabbour A, Keogh A, Hayward C, Macdonald P. Chronic sildenafil lowers transpulmonary gradient and improves cardiac output allowing successful heart transplantation. Eur J Heart Fail. 2007;9(6–7):674–7. https://doi.org/10.1016/j.ejheart.2007.01.008.

    Article  CAS  PubMed  Google Scholar 

  113. Lewis GD, Lachmann J, Camuso J, Lepore JJ, Shin J, Martinovic ME, et al. Sildenafil improves exercise hemodynamics and oxygen uptake in patients with systolic heart failure. Circulation. 2007;115(1):59–66. https://doi.org/10.1161/CIRCULATIONAHA.106.626226.

    Article  CAS  PubMed  Google Scholar 

  114. Lewis GD, Shah R, Shahzad K, Camuso JM, Pappagianopoulos PP, Hung J, et al. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation. 2007;116(14):1555–62. https://doi.org/10.1161/CIRCULATIONAHA.107.716373.

    Article  CAS  PubMed  Google Scholar 

  115. Tedford RJ, Hemnes AR, Russell SD, Wittstein IS, Mahmud M, Zaiman AL, et al. PDE5A inhibitor treatment of persistent pulmonary hypertension after mechanical circulatory support. Circulation Heart failure. 2008;1(4):213–9. https://doi.org/10.1161/CIRCHEARTFAILURE.108.796789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Grimminger F, Weimann G, Frey R, Voswinckel R, Thamm M, Bolkow D, et al. First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension. Eur Respir J. 2009;33(4):785–92. https://doi.org/10.1183/09031936.00039808.

    Article  CAS  PubMed  Google Scholar 

  117. Bonderman D, Ghio S, Felix SB, Ghofrani HA, Michelakis E, Mitrovic V, et al. Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction: a phase IIb double-blind, randomized, placebo-controlled, dose-ranging hemodynamic study. Circulation. 2013;128(5):502–11. https://doi.org/10.1161/CIRCULATIONAHA.113.001458.

    Article  CAS  PubMed  Google Scholar 

  118. Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CSP, Maggioni AP, et al. Effect of vericiguat, a soluble guanylate cyclase stimulator, on natriuretic peptide levels in patients with worsening chronic heart failure and reduced ejection fraction: the SOCRATES-REDUCED randomized trial. JAMA. 2015;314(21):2251–62. https://doi.org/10.1001/jama.2015.15734.

    Article  CAS  PubMed  Google Scholar 

  119. Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383–92. https://doi.org/10.1056/NEJMoa1313731.

    Article  CAS  PubMed  Google Scholar 

  120. Redfield MM, Anstrom KJ, Levine JA, Koepp GA, Borlaug BA, Chen HH, et al. Isosorbide mononitrate in heart failure with preserved ejection fraction. N Engl J Med. 2015;373(24):2314–24. https://doi.org/10.1056/NEJMoa1510774.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Guazzi M, Vicenzi M, Arena R, Guazzi MD. Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study. Circulation. 2011;124(2):164–74. https://doi.org/10.1161/CIRCULATIONAHA.110.983866.

    Article  CAS  PubMed  Google Scholar 

  122. Hoendermis ES, Liu LCY, Hummel YM, van der Meer P, de Boer RA, Berger RMF, et al. Effects of sildenafil on invasive haemodynamics and exercise capacity in heart failure patients with preserved ejection fraction and pulmonary hypertension: a randomized controlled trial. Eur Heart J. 2015;36(38):2565–73. https://doi.org/10.1093/eurheartj/ehv336.

    Article  CAS  PubMed  Google Scholar 

  123. Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, et al. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013;309(12):1268–77. https://doi.org/10.1001/jama.2013.2024.

    Article  CAS  PubMed  Google Scholar 

  124. Borlaug BA, Lewis GD, McNulty SE, Semigran MJ, LeWinter M, Chen H, et al. Effects of sildenafil on ventricular and vascular function in heart failure with preserved ejection fraction. Circ Heart Fail. 2015;8(3):533–41. https://doi.org/10.1161/CIRCHEARTFAILURE.114.001915.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Bonderman D, Pretsch I, Steringer-Mascherbauer R, Jansa P, Rosenkranz S, Tufaro C, et al. Acute hemodynamic effects of riociguat in patients with pulmonary hypertension associated with diastolic heart failure (DILATE-1): a randomized, double-blind, placebo-controlled, single-dose study. Chest. 2014;146(5):1274–85. https://doi.org/10.1378/chest.14-0106.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Filippatos G, Maggioni AP, Lam CSP, Pieske-Kraigher E, Butler J, Spertus J, et al. Patient-reported outcomes in the SOluble guanylate cyclase stimulatoR in heArT failurE patientS with PRESERVED ejection fraction (SOCRATES-PRESERVED) study. Eur J Heart Fail. 2017;19(6):782–91. https://doi.org/10.1002/ejhf.800.

    Article  CAS  PubMed  Google Scholar 

  127. Zile MR, Bourge RC, Redfield MM, Zhou D, Baicu CF, Little WC. Randomized, double-blind, placebo-controlled study of sitaxsentan to improve impaired exercise tolerance in patients with heart failure and a preserved ejection fraction. JACC Heart Fail. 2014;2(2):123–30. https://doi.org/10.1016/j.jchf.2013.12.002.

    Article  PubMed  Google Scholar 

  128. Koller B, Steringer-Mascherbauer R, Ebner CH, Weber T, Ammer M, Eichinger J, et al. Pilot study of endothelin receptor blockade in heart failure with diastolic dysfunction and pulmonary hypertension (BADDHY-trial). Heart Lung Circ. 2017;26(5):433–41. https://doi.org/10.1016/j.hlc.2016.09.004.

    Article  CAS  PubMed  Google Scholar 

  129. Vachiery JL, et al. Macitentan in pulmonary hypertension due to left ventricular dysfunction. Eur Respir J. 2018; in press

Download references

Author information

Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, Medical University of South Carolina (MUSC), Strom Thurmond Gazes Building, Room 215, 114 Doughty St/MSC592, Charleston, SC, 29425, USA

    Bhavadharini Ramu, Brian A. Houston & Ryan J. Tedford

Authors
  1. Bhavadharini Ramu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian A. Houston
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ryan J. Tedford
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ryan J. Tedford.

Ethics declarations

Conflict of Interest

Bhavadharini Ramu and Brian A. Houston declare no conflicts of interest.

Ryan J. Tedford reports personal fees from Actelion (Johnson and Johnson) and personal fees from St. Jude Medical (Abbott) outside the submitted work.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Pharmacologic Therapy

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ramu, B., Houston, B.A. & Tedford, R.J. Pulmonary Vascular Disease: Hemodynamic Assessment and Treatment Selection—Focus on Group II Pulmonary Hypertension. Curr Heart Fail Rep 15, 81–93 (2018). https://doi.org/10.1007/s11897-018-0377-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11897-018-0377-9

Keywords

Search

Navigation