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Review article: Biomedical intelligence

Vol. 147 No. 0304 (2017)

Pulmonary hypertension associated with left-sided heart disease

Cite this as:
Swiss Med Wkly. 2017;147:w14395
Published
17.01.2017

Summary

Pulmonary hypertension associated with left-sided heart disease (PH-LHD) is the most common type of pulmonary hypertension. In patients with left-sided heart disease, the presence of pulmonary hypertension is typically a marker of more advanced disease, more severe symptoms, and worse prognosis. In contrast to pulmonary arterial hypertension, PH-LHD is characterised by an elevated pulmonary artery wedge pressure (postcapillary pulmonary hypertension) without or with an additional precapillary component (isolated postcapillary vs combined postcapillary and precapillary pulmonary hypertension). Transthoracic echocardiography is the primary noninvasive imaging tool to estimate the probability of pulmonary hypertension and to establish a working diagnosis on the mechanism of pulmonary hypertension. However, right heart catheterisation is always required if significant pulmonary hypertension is suspected and exact knowledge of the haemodynamic constellation is necessary. The haemodynamic constellation (mean pulmonary artery pressure, mean pulmonary artery wedge pressure, left ventricular end-diastolic pressure) in combination with clinical information and imaging findings (mainly echocardiography, coronary angiography and cardiac magnetic resonance imaging) will usually allow the exact mechanism underlying PH-LHD to be defined, which is a prerequisite for appropriate treatment. The general principle for the management of PH-LHD is to treat the underlying left-sided heart disease in an optimal manner using drugs and/or interventional or surgical therapy. There is currently no established indication for pulmonary arterial hypertension-specific therapies in PH-LHD, and specific therapies may even cause harm in patients with PH-LHD.

References

  1. Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): 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. doi:.https://doi.org/10.1093/eurheartj/ehv317
  2. Maeder MT, Kleiner R, Weilenmann D, Schoch OD. Pulmonary hypertension associated with left heart and lung diseases. Cardiovasc Med. 2014;17:320–7.
  3. Rosenkranz S, Gibbs JS, Wachter R, De Marco T, Vonk-Noordegraaf A, Vachiéry JL. Left ventricular heart failure and pulmonary hypertension. Eur Heart J. 2016;37(12):942–54. doi:.https://doi.org/10.1093/eurheartj/ehv512
  4. 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(25, Suppl):D100–8. doi:.https://doi.org/10.1016/j.jacc.2013.10.033
  5. Maeder MT, Kleiner R, Weilenmann D. Severely worsening dyspnea after initiation of macitentan therapy for pulmonary arterial hypertension. Int J Cardiol. 2016;202:244–5. doi:.https://doi.org/10.1016/j.ijcard.2015.08.132
  6. Boilson BA, Schirger JA, Borlaug BA. Caveat medicus! Pulmonary hypertension in the elderly: a word of caution. Eur J Heart Fail. 2010;12(1):89–93. doi:.https://doi.org/10.1093/eurjhf/hfp171
  7. 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. doi:.https://doi.org/10.1164/rccm.201503-0529OC
  8. Lam CS, Roger VL, Rodeheffer RJ, Borlaug BA, Enders FT, Redfield MM. Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study. J Am Coll Cardiol. 2009;53(13):1119–26. doi:.https://doi.org/10.1016/j.jacc.2008.11.051
  9. Abramson SV, Burke JF, Kelly JJ, Jr, Kitchen JG, 3rd, Dougherty MJ, Yih DF, et al. Pulmonary hypertension predicts mortality and morbidity in patients with dilated cardiomyopathy. Ann Intern Med. 1992;116(11):888–95. doi:.https://doi.org/10.7326/0003-4819-116-11-888
  10. Ghio S, Gavazzi A, Campana C, Inserra C, Klersy C, Sebastiani R, et al. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol. 2001;37(1):183–8. doi:.https://doi.org/10.1016/S0735-1097(00)01102-5
  11. Mentias A, Patel K, Patel H, Gillinov AM, Sabik JF, Mihaljevic T, et al. Effect of Pulmonary Vascular Pressures on Long-Term Outcome in Patients With Primary Mitral Regurgitation. J Am Coll Cardiol. 2016;67(25):2952–61. doi:.https://doi.org/10.1016/j.jacc.2016.03.589
  12. 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. doi:.https://doi.org/10.1016/j.jtcvs.2006.08.104
  13. Etz CD, Welp HA, Tjan TD, Hoffmeier A, Weigang E, Scheld HH, et al. Medically refractory pulmonary hypertension: treatment with nonpulsatile left ventricular assist devices. Ann Thorac Surg. 2007;83(5):1697–705. doi:.https://doi.org/10.1016/j.athoracsur.2007.01.019
  14. Melenovsky V, Hwang SJ, Lin G, Redfield MM, Borlaug BA. Right heart dysfunction in heart failure with preserved ejection fraction. Eur Heart J. 2014;35(48):3452–62. doi:.https://doi.org/10.1093/eurheartj/ehu193
  15. Borlaug BA, Kane GC, Melenovsky V, Olson TP. Abnormal right ventricular-pulmonary artery coupling with exercise in heart failure with preserved ejection fraction. Eur Heart J. 2016;ehw241; epub ahead of print. doi:.https://doi.org/10.1093/eurheartj/ehw241
  16. Kammerlander AA, Marzluf BA, Graf A, Bachmann A, Kocher A, Bonderman D, et al. Right ventricular dysfunction, but not tricuspid regurgitation, is associated with outcome late after left heart valve procedure. J Am Coll Cardiol. 2014;64(24):2633–42. doi:.https://doi.org/10.1016/j.jacc.2014.09.062
  17. Galiè N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, et al.; ESC Committee for Practice Guidelines (CPG). Guidelines for the diagnosis and treatment of pulmonary hypertension: the 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 the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J. 2009;30(20):2493–537. doi:.https://doi.org/10.1093/eurheartj/ehp297
  18. Gerges C, Gerges M, Lang MB, Zhang Y, Jakowitsch J, Probst P, et al. Diastolic pulmonary vascular pressure gradient: a predictor of prognosis in “out-of-proportion” pulmonary hypertension. Chest. 2013;143(3):758–66. doi:.https://doi.org/10.1378/chest.12-1653
  19. 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. doi:.https://doi.org/10.1016/j.healun.2013.11.008
  20. Tampakakis E, Leary PJ, Selby VN, De Marco T, Cappola TP, Felker GM, 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. doi:.https://doi.org/10.1016/j.jchf.2014.07.010
  21. Guazzi M, Borlaug BA. Pulmonary hypertension due to left heart disease. Circulation. 2012;126(8):975–90. doi:.https://doi.org/10.1161/CIRCULATIONAHA.111.085761
  22. Gerges M, Gerges C, Lang IM. How to define pulmonary hypertension due to left heart disease. Eur Respir J. 2016;48(2):553–5. doi:.https://doi.org/10.1183/13993003.00432-2016
  23. McGoon M, Gutterman D, Steen V, Barst R, McCrory DC, Fortin TA, et al.; American College of Chest Physicians. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004;126(1, Suppl):14S–34S. doi:.https://doi.org/10.1378/chest.126.1_suppl.14S
  24. Rich JD, Shah SJ, Swamy RS, Kamp A, Rich S. Inaccuracy of Doppler echocardiographic estimates of pulmonary artery pressures in patients with pulmonary hypertension: implications for clinical practice. Chest. 2011;139(5):988–93. doi:.https://doi.org/10.1378/chest.10-1269
  25. Testani JM, St John Sutton MG, Wiegers SE, Khera AV, Shannon RP, Kirkpatrick JN. Accuracy of noninvasively determined pulmonary artery systolic pressure. Am J Cardiol. 2010;105(8):1192–7. doi:.https://doi.org/10.1016/j.amjcard.2009.11.048
  26. Chemla D, Castelain V, Humbert M, Hébert JL, Simonneau G, Lecarpentier Y, et al. New formula for predicting mean pulmonary artery pressure using systolic pulmonary artery pressure. Chest. 2004;126(4):1313–7. doi:.https://doi.org/10.1378/chest.126.4.1313
  27. Simon MA, Rajagopalan N, Mathier MA, Shroff SG, Pinsky MR, López-Candales A. Tissue Doppler imaging of right ventricular decompensation in pulmonary hypertension. Congest Heart Fail. 2009;15(6):271–6. doi:.https://doi.org/10.1111/j.1751-7133.2009.00113.x
  28. Mullens W, Borowski AG, Curtin RJ, Thomas JD, Tang WH. Tissue Doppler imaging in the estimation of intracardiac filling pressure in decompensated patients with advanced systolic heart failure. Circulation. 2009;119(1):62–70. doi:.https://doi.org/10.1161/CIRCULATIONAHA.108.779223
  29. 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. doi:.https://doi.org/10.1161/CIRCHEARTFAILURE.110.958801
  30. Opotowsky AR, Ojeda J, Rogers F, Prasanna V, Clair M, Moko L, et al. A simple echocardiographic prediction rule for hemodynamics in pulmonary hypertension. Circ Cardiovasc Imaging. 2012;5(6):765–75. doi:.https://doi.org/10.1161/CIRCIMAGING.112.976654
  31. D’Alto M, Romeo E, Argiento P, Pavelescu A, Mélot C, D’Andrea A, et al. Echocardiographic prediction of pre- versus postcapillary pulmonary hypertension. J Am Soc Echocardiogr. 2015;28(1):108–15. doi:.https://doi.org/10.1016/j.echo.2014.09.004
  32. Bonderman D, Wexberg P, Heinzl H, Lang IM. Non-invasive algorithms for the diagnosis of pulmonary hypertension. Thromb Haemost. 2012;108(6):1037–41. doi:.https://doi.org/10.1160/TH12-04-0239
  33. Abbas AE, Fortuin FD, Schiller NB, Appleton CP, Moreno CA, Lester SJ. A simple method for noninvasive estimation of pulmonary vascular resistance. J Am Coll Cardiol. 2003;41(6):1021–7. doi:.https://doi.org/10.1016/S0735-1097(02)02973-X
  34. Maeder MT, Karapanagiotidis S, Dewar EM, Gamboni SE, Htun N, Kaye DM. Accuracy of Doppler echocardiography to estimate key hemodynamic variables in subjects with normal left ventricular ejection fraction. J Card Fail. 2011;17(5):405–12. doi:.https://doi.org/10.1016/j.cardfail.2010.12.003
  35. 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. doi:.https://doi.org/10.1016/j.jacc.2013.10.032
  36. 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. doi:.https://doi.org/10.1016/j.jacc.2010.04.040
  37. 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. doi:.https://doi.org/10.1161/CIRCHEARTFAILURE.113.000468
  38. Borlaug BA, Nishimura RA, Sorajja P, Lam CS, Redfield MM. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ Heart Fail. 2010;3(5):588–95. doi:.https://doi.org/10.1161/CIRCHEARTFAILURE.109.930701
  39. Herve P, Lau EM, Sitbon O, Savale L, Montani D, Godinas L, et al. Criteria for diagnosis of exercise pulmonary hypertension. Eur Respir J. 2015;46(3):728–37. doi:.https://doi.org/10.1183/09031936.00021915
  40. 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(9):809–18. doi:.https://doi.org/10.1056/NEJMoa1213917
  41. Buser M, Felizeter-Kessler M, Lenggenhager D, Maeder MT. Rapidly progressive pulmonary hypertension in a patient with pulmonary tumor thrombotic microangiopathy. Am J Respir Crit Care Med. 2015;191(6):711–2. doi:.https://doi.org/10.1164/rccm.201501-0004IM
  42. Gibson DN, Di Biase L, Mohanty P, Patel JD, Bai R, Sanchez J, et al. Stiff left atrial syndrome after catheter ablation for atrial fibrillation: clinical characterization, prevalence, and predictors. Heart Rhythm. 2011;8(9):1364–71. doi:.https://doi.org/10.1016/j.hrthm.2011.02.026
  43. Maeder MT, Kaye DM. Heart failure with normal left ventricular ejection fraction. J Am Coll Cardiol. 2009;53(11):905–18. doi:.https://doi.org/10.1016/j.jacc.2008.12.007
  44. Paulus WJ, Tschöpe C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J. 2007;28(20):2539–50. doi:.https://doi.org/10.1093/eurheartj/ehm037
  45. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al.; Authors/Task Force Members. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129–200. doi:.https://doi.org/10.1093/eurheartj/ehw128
  46. 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. doi:.https://doi.org/10.1016/S0002-8703(97)70105-4
  47. 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. doi:.https://doi.org/10.1016/j.cardfail.2004.05.006
  48. Kalra PR, Moon JC, Coats AJ. Do results of the ENABLE (Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure) study spell the end for non-selective endothelin antagonism in heart failure? Int J Cardiol. 2002;85(2-3):195–7. doi:.https://doi.org/10.1016/S0167-5273(02)00182-1
  49. Lüscher TF, Enseleit F, Pacher R, Mitrovic V, Schulze MR, Willenbrock R, et al.; Heart Failure ET(A) Receptor Blockade Trial. 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. doi:.https://doi.org/10.1161/01.CIR.0000038497.80095.E1
  50. Anand I, McMurray J, Cohn JN, Konstam MA, Notter T, Quitzau K, et al.; EARTH investigators. 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. doi:.https://doi.org/10.1016/S0140-6736(04)16723-8
  51. Guazzi M, Tumminello G, Di Marco F, Fiorentini C, Guazzi MD. The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure. J Am Coll Cardiol. 2004;44(12):2339–48. doi:.https://doi.org/10.1016/j.jacc.2004.09.041
  52. 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. doi:.https://doi.org/10.1161/CIRCULATIONAHA.107.716373
  53. Bonderman D, Ghio S, Felix SB, Ghofrani HA, Michelakis E, Mitrovic V, et al.; Left Ventricular Systolic Dysfunction Associated With Pulmonary Hypertension Riociguat Trial (LEPHT) Study Group. 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. doi:.https://doi.org/10.1161/CIRCULATIONAHA.113.001458
  54. Cooper TJ, Guazzi M, Al-Mohammad A, Amir O, Bengal T, Cleland JG, et al. Sildenafil in Heart failure (SilHF). An investigator-initiated multinational randomized controlled clinical trial: rationale and design. Eur J Heart Fail. 2013;15(1):119–22. doi:.https://doi.org/10.1093/eurjhf/hfs152
  55. 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. doi:.https://doi.org/10.1161/CIRCULATIONAHA.110.983866
  56. Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, et al.; RELAX Trial. 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. doi:.https://doi.org/10.1001/jama.2013.2024
  57. Hoendermis ES, Liu LC, Hummel YM, van der Meer P, de Boer RA, Berger RM, 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. doi:.https://doi.org/10.1093/eurheartj/ehv336
  58. 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. doi:.https://doi.org/10.1378/chest.14-0106
  59. Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Barón-Esquivias G, Baumgartner H, et al.; Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012). Eur Heart J. 2012;33(19):2451–96. doi:.https://doi.org/10.1093/eurheartj/ehs109
  60. Maeder MT, Rickli H. Herzinsuffizienz mit erhaltener linksventrikulärer Auswurffraktion. [Heart failure with preserved left ventricular ejection fraction] Praxis (Bern). 2013;102(21):1299–307. Article in German. doi:.https://doi.org/10.1024/1661-8157/a001439
  61. Hasenfuß G, Hayward C, Burkhoff D, Silvestry FE, McKenzie S, Gustafsson F, et al.; REDUCE LAP-HF study investigators. A transcatheter intracardiac shunt device for heart failure with preserved ejection fraction (REDUCE LAP-HF): a multicentre, open-label, single-arm, phase 1 trial. Lancet. 2016;387(10025):1298–304. doi:.https://doi.org/10.1016/S0140-6736(16)00704-2