Abstract
Patients with inoperable chronic thromboembolic pulmonary hypertension (Inop-CTEPH) treated with conventional therapy have a poor survival. We compare the 3-year survival between those treated with conventional therapy and those treated with conventional therapy and a combination of novel drugs. We also evaluate the clinical course. A total of 34 Inop-CTEPH consecutive patients were evaluated from 1991 to 2009 including right heart catheterization (RHC) and perfusion lung scan (PLS): 7 underwent surgical treatment while 27 were confirmed inoperable. Of these 27 patients, 12 evaluated from 1991 to 2003 (Group 1) were treated with conventional therapy and 15 evaluated from 2004 to 2009 (Group 2) were treated with conventional and novel therapies. At baseline, no group difference emerged at RHC. Based on clinical course, novel drugs and oxygen supplementation were given to patients of Group 2. Seven of these who had worse clinical course repeated RHC and four of them also PLS during therapy. Those without repeat RHC had baseline pulmonary artery mean pressure and brain natriuretic peptide (NT-proBNP) lower and mixed venous saturation (SvO2) and exercise test higher (p = 0.022, 0.015, 0.044 and 0.003, respectively). During therapy, those with repeat RHC had total pulmonary vascular resistance reduced (p = 0.012), base excess increased (p = 0.002) and significant redistribution of pulmonary blood flow at PLS. At the 3-year follow-up, survival was 86% in Group 2 and 31% in Group 1 (p = 0.031). In Inop-CTEPH patients, the clinical course may help to select drugs and the level of oxygen supply that can improve hemodynamics, gas exchange and long-term survival.
Similar content being viewed by others
References
Moser KM, Houk VN, Jones RC, Hufnagel CC (1965) Chronic, massive thrombotic obstruction of the pulmonary arteries: analysis of four operated cases. Circulation 32:377–385
Moor GF, Sabiston DC Jr (1969) Embolectomy for chronic PE and pulmonary hypertension. Rev Surg 26:449–451
Riedel M, Stanek V, Widimsky J, Prerovsky I (1982) Longterm follow-up of patients with pulmonary thromboembolism: late prognosis and evolution of hemodynamic and respiratory data. Chest 81:151–158
Dartevelle P, Fadel E, Mussot S, Chapelier A, Hervé P, de Perrot M, Cerrina J, Ladurie FL, Lehouerou D, Humbert M, Sitbon O, Simonneau G (2004) Chronic thromboembolic pulmonary hypertension. Eur Respir J 23:637–648
Auger WR, Kerr KM, Kim NH, Ben-Yehuda O, Knowlton KU, Fedullo PF (2004) Chronic thromboembolic pulmonary hypertension. CardiolClin 22:453–466
Hoeper MM, Mayer E, Simonneau G, Rubin LJ (2006) Chronic thromboembolic pulmonary hypertension. Circulation 113:2011–2020
Jamieson SW, Auger WR, Fedullo PF, Channick RN, Kriett JM, Tarazi RY, Moser KM (1993) Experience and results with 150 pulmonary thromboendarterectomy operations over a 29-months period. J Thorac Cardiovasc Surg 106:116–126
Galiè N, Kim NHS (2006) Pulmonary microvascular disease in chronic thromboembolic pulmonary hypertension. Proc Am Thorac Soc 3:571–576
Bresser P, Pepke-Zaba J, Jaïs X, Humbert M, Hoeper MM (2006) Medical therapies for chronic thromboembolic pulmonary hypertension an evolving treatment paradigm. Proc Am Thorac Soc 3:594–600
Lewczuk J, Piszko P, Jagas J, Porada A, Wójciak S, Sobkowicz B, Wrabec K (2001) Prognostic factors in medically treated patients with chronic pulmonary embolism. Chest 119:818–823
Hoeper MM, Marckevych I, Spiekerkoetter E, Welte T, Niedermeyer J (2005) Goal-oriented treatment and combination therapy for pulmonary arterial hypertension. Eur Respir J26:858–863
Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, Elliot CG, Gaine SP, Gladwin MT, Jing Z-C, Krowka MJ, Langleben D, Nakanishi N, Souza R (2009) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 54(Suppl 1):43–54
Reichenberger F, Voswinckel R, Enke B, Rutsch M, El Fechtali E, Schmehl T, Olschewski H, Schermuly R, Weissmann N, Ghofrani HA, Grimminger F, Mayer E, Seeger W (2007) Long-term treatment with sildenafil in chronic thromboembolic pulmonary hypertension. Eur Respr J30:922–927
Condliffe R, Kiely DG, Gibbs JSR, Corris PA, Peacock AJ, Jenkins DP, Hodgkins D, Goldsmith K, Hughes RJ, Sheares K, Tsui SSL, Armstrong IJ, Torpy C, Crackett R, Carlin CM, Das C, Coghlan GJ, Pepke-Zaba J (2008) Improved outcomes in medically and surgically treated chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med 177:1122–1127
Hughes RJ, Jaïs X, Bonderman D, Suntharalingam J, Hunbert M, Lang I, Simonneau G, Pepke-Zaba J (2006) The efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension: a 1-year follow-up study. Eur Respir J28:138–143
Jaïs X, D’Armini AM, Jansa P, Torbicki A, Delcroix M, Ghofrani HA, Hoeper MM, Lang IM, Mayer E, Pepke-Zaba J, Perchenet L, Morganti A, Simonneau G, Rubin LJ (2008) Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension. BENEFiT a Randomized, Placebo-Controlled Trial. J Am Coll Cardio l52:2127–2134
Seyfarth H-J, Halank M, Wilkens H, Schäfers H-J, Ewert R, Riedel M, Schuster E, Pankau H, Hammerschmidt S, Wirtz H (2010) Standard PAH therapy improves lomg term survival in CTEPH. Clin Res Cardiol 99:553–556
Rubin LJ, Hoeper MM, Klepetko W, Galiè N, Lang IM, Simonneau G (2006) Current and future management of chronic thromboembolic pulmonary hypertension. From diagnosis to treatment responses. Proc Am Thorac Soc 3:601–607
Miniati M, Pistolesi M, Marini C, DiRicco G, Formichi B, Predilett R, Allescia G, Tonelli L, Sostman HD, Giuntini C (1996) Value of perfusion lung scan in the diagnosis of pulmonary embolism: results of the prospective investigative study of acute pulmonary embolism diagnosis (PISA-PED). Am J RespirCrit Care Med 154:1387–1393
Severinghaus JW (1979) Simple, accurate equations for human blood O2 dissociation computations. J Appl Physiol 46:599–602
ESC/ERS Guidelines for the diagnosis, treatment of pulmonary hypertension (2009) Eur Heart J30:2493–2537
Altman DG (1991) Practical statistics for medical research. Chapman & Hall, London, p 230
Barst RJ, Gibbs SR, Ghofrani HA, Hoeper MM, McLaughlin VV, Rubin LJ, Sitbon O, Tapson VF, Galiè N (2009) Updated evidence-based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol 54(Suppl 1):78–84
Moser KM, Bloor CM (1993) Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension. Chest 103:685–692
Ono F, Nagaya N, Okumura H et al (2003) Effect of orally active prostacyclin analogue on survival in patients with chronic thromboembolic pulmonary hypertension without major vessel obstruction. Chest 123:1583–1588
Ghofrani HA, Schermuly RT, Rose F, Wiedemann R, Kohstall MG, Kreckel A, Olschewski H, Weissmann N, Enke B, Ghofrani S, Seeger W, Grimminger F (2003) Sildenafil for long-term treatment of nonoperable chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med 167:1139–1141
Braunwald E (2001) Normal and abnormal myocardial function. In: Harrison’s Principles of internal medicine, 15thedn. McGraw-Hill, New York, pp 1309–1318
Naeije R (2010) The 6-min walk distance in pulmonary arterial hypertension: “Je t’aime, moi non plus”. Chest 137:1258–1260
Braunwald E (2001) Hypoxia and cyanosis. In: Harrison’s Principles of internal medicine, 15thedn. McGraw-Hill, New York, pp 214–217
Becattini C, Manina G, Busti C, Gennarini S, Agnelli G (2010) Bosentan for chronic thromboembolic pulmonary hypertension: findings from a systematic review and meta-analysis. Thromb Res 126(1):e51–e56
Croxton TL, Bailey WC, For the NHLBI working Group on Long-term Oxygen Treatment in COPD et al (2006) Long-term oxygen treatment in chronic obstructive pulmonary disease: recommendations for future research. Am J Respir Crit Care Med 174:373–378
Kapitan KS, Buchbinder M, Wagner PD, Moser KM (1989) Mechanisms of hypoxemia in chronic thromboembolic pulmonary hypertension. Am Rev Respir Dis 139:1149–1154
Santolicandro A, Prediletto R, Fornai E, Formichi B, Begliomini E, Giannella-Neto A, Giuntini C (1995) Mechanisms of hypoxemia and hypocapnia in pulmonary embolism. Am J Respir Crit Care Med 152:336–347
Acknowledgments
We thank Drs. Roberta Pancani and EdoardoAirò for collecting patient data.
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Marini, C., Formichi, B., Bauleo, C. et al. Improved survival in patients with inoperable chronic thromboembolic pulmonary hypertension. Intern Emerg Med 8, 307–316 (2013). https://doi.org/10.1007/s11739-011-0610-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11739-011-0610-y