G Model
JJCC-1136; No. of Pages 5 Journal of Cardiology xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Journal of Cardiology journal homepage: www.elsevier.com/locate/jjcc
Original article
Pulmonary hypertension due to left heart disease: The prognostic implications of diastolic pulmonary vascular pressure gradient Tatsuro Ibe (MD), Hiroshi Wada (MD, FJCC)*, Kenichi Sakakura (MD), Nahoko Ikeda (MD), Yoko Yamada (MD), Yoshitaka Sugawara (MD), Takeshi Mitsuhashi (MD, FJCC), Junya Ako (MD), Hideo Fujita (MD, FJCC), Shin-ichi Momomura (MD, FJCC) Division of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 April 2015 Received in revised form 18 July 2015 Accepted 23 July 2015 Available online xxx
Background: Compared to transpulmonary pressure gradient (TPPG), diastolic pulmonary vascular pressure gradient (DPG) may be a more sensitive and specific indicator for pulmonary hypertension (PH) due to left heart disease (LHD) with significant pulmonary vascular disease (PVD). The aim of this study was to investigate the incidence and clinical features of PH-LHD with PVD classified by DPG and TPPG. Methods: We analyzed 410 patients admitted for symptomatic heart failure (HF) (New York Heart Association 2) and who underwent right heart catheterization (RHC) at compensated stage between 2007 and 2012. Patients with PH-LHD were divided into 3 groups according to the value of DPG and TPPG (Non-PVD group: DPG 15 mmHg at rest were defined as PH-LHD. These patients were divided into 3 groups by DPG and TPPG. The definition of DPG was the difference between diastolic pulmonary artery pressure (dPAP) and PAWP (dPAP–PAWP), whereas the definition of TPPG was the difference between mPAP and PAWP (mPAP–PAWP). Three groups divided by the value of DPG and TPPG were as follows: (i) Non-PVD group: DPG 50 mm) Elevated BNP (>600 pg/ml)
1.89 3.57 1.49 0.98 0.17 1.83 1.50
0.77 1.33 0.75 0.18 0.04 0.24 0.72
to to to to to to to
p-value 4.64 9.55 2.99 5.32 0.65 14.2 3.15
0.17 0.01 0.26 0.98 0.01 0.57 0.28
PVD, pulmonary vascular disease; TPPG, transpulmonary pressure gradient; DPG, diastolic pulmonary vascular pressure gradient; mRAP, mean right atrial pressure; LV dysfunction, left ventricular dysfunction; LVDd, left ventricular diastolic dimension; LVDs, left ventricular systolic dimension; BNP, brain natriuretic peptide.
dimension was a better clinical indicator, which is usually considered as a worse clinical indicator [21]. However, in PH population, increased right ventricle (RV) afterload gradually results in RV dilation, and leftward septal shift [22]. It might be the reason why dilated LVDd was associated with better clinical outcomes in patients with PH-LHD. Previously, TPPG had been used as the definition of PH-LHD with PVD (reactive post-capillary PH), and some studies used this definition to evaluate the efficacy of pulmonary vasodilators for patients with PH-LHD. PDE-5 inhibitors such as sildenafil improved clinical status, exercise capacity, and cardiac function in HF patients [23,24], but they were not able to improve prognosis and rate of hospital readmission [25]. There might be the possibility of over- and underestimation about PH-LHD with PVD. Study limitations This is a retrospective and small sample study in a single tertiary center. The patients who were hospitalized in our center might be highly selected. The incidence and clinical features of the DPG-PVD group could vary depending on study patients. Therefore, the present study has an inherent patient selection bias. There is a possibility of incomplete follow-up because clinical follow-up was performed via office visit. Heart rhythm (sinus rhythm or not) might affect the measurements of RHC as well as echocardiography. Further prospective large-sample studies and dedicated pathological evaluation are warranted. Conclusions PH-LHD with PVD classified by DPG was significantly associated with poor long-term clinical outcomes, whereas the association between PH-LHD with PVD classified by TPPG and clinical outcomes did not reach statistical significance. However, further studies are needed, because there was no substantial difference in clinical outcomes between PH-LHD with PVD classified by DPG and PH-LHD with PVD classified by TPPG. Conflict of interest The authors declare that there is no conflict of interest. References [1] Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, Elliott CG, Gaine SP, Gladwin MT, Jing ZC, Krowka MJ, Langleben D, Nakanishi N, Souza R. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2009;54:S43–54.
5
[2] D’Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, Levy PS, Pietra GG, Reid LM, Reeves JT, Rich S, et al. Survival in patients with primary pulmonary hypertension, Results from a national prospective registry. Ann Intern Med 1991;115:343–9. [3] Matsubara H, Ogawa A. Treatment of idiopathic/hereditary pulmonary arterial hypertension. J Cardiol 2014;64:243–9. [4] Grigioni F, Potena L, Galie N, Fallani F, Bigliardi M, Coccolo F, Magnani G, Manes A, Barbieri A, Fucili A, Magelli C, Branzi A. Prognostic implications of serial assessments of pulmonary hypertension in severe chronic heart failure. J Heart Lung Transplant 2006;25:1241–6. [5] Tatebe S, Fukumoto Y, Sugimura K, Miyamichi-Yamamoto S, Aoki T, Miura Y, Nochioka K, Satoh K, Shimokawa H. Clinical significance of reactive postcapillary pulmonary hypertension in patients with left heart disease. Circ J 2012;76:1235–44. [6] Aronson D, Eitan A, Dragu R, Burger AJ. Relationship between reactive pulmonary hypertension and mortality in patients with acute decompensated heart failure. Circ Heart Fail 2011;4:644–50. [7] Naeije R, Vachiery JL, Yerly P, Vanderpool R. The transpulmonary pressure gradient for the diagnosis of pulmonary vascular disease. Eur Respir J 2013;41:217–23. [8] Shiba N, Watanabe J, Shinozaki T, Koseki Y, Sakuma M, Kagaya Y, Shirato K. Poor prognosis of Japanese patients with chronic heart failure following myocardial infarction – comparison with nonischemic cardiomyopathy. Circ J 2005;69:143–9. [9] Bonow RO, Lakatos E, Maron BJ, Epstein SE. Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventricular systolic function. Circulation 1991;84:1625–35. [10] Guglin M, Khan H. Pulmonary hypertension in heart failure. J Card Fail 2010;16:461–74. [11] Fang JC, DeMarco T, Givertz MM, Borlaug BA, Lewis GD, Rame JE, GombergMaitland M, Murali S, Frantz RP, McGlothlin D, Horn EM, Benza RL. 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;31:913–33. [12] Guazzi M, Borlaug BA. Pulmonary hypertension due to left heart disease. Circulation 2012;126:975–90. [13] Robbins IM, Newman JH, Johnson RF, Hemnes AR, Fremont RD, Piana RN, Zhao DX, Byrne DW. Association of the metabolic syndrome with pulmonary venous hypertension. Chest 2009;136:31–6. [14] Leung CC, Moondra V, Catherwood E, Andrus BW. Prevalence and risk factors of pulmonary hypertension in patients with elevated pulmonary venous pressure and preserved ejection fraction. Am J Cardiol 2010;106: 284–6. [15] 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;53:1119–26. [16] Bursi F, McNallan SM, Redfield MM, Nkomo VT, Lam CS, Weston SA, Jiang R, Roger VL. Pulmonary pressures and death in heart failure: a community study. J Am Coll Cardiol 2012;59:222–31. [17] Damy T, Goode KM, Kallvikbacka-Bennett A, Lewinter C, Hobkirk J, Nikitin NP, Dubois-Rande JL, Hittinger L, Clark AL, Cleland JG. Determinants and prognostic value of pulmonary arterial pressure in patients with chronic heart failure. Eur Heart J 2010;31:2280–90. [18] Lee JH, IM Cho K. Arterial stiffness, antiphospholipid antibodies, and pulmonary arterial hypertension in systemic lupus erythematosus. J Cardiol 2014;64:450–5. [19] Gerges C, Gerges M, Lang MB, Zhang Y, Jakowitsch J, Probst P, Maurer G, Lang IM. Diastolic pulmonary vascular pressure gradient: a predictor of prognosis in out-of-proportion pulmonary hypertension. Chest 2013;143:758–66. [20] Gheorghiade M, De Luca L, Fonarow GC, Filippatos G, Metra M, Francis GS. Pathophysiologic targets in the early phase of acute heart failure syndromes. Am J Cardiol 2005;96:11G–7G. [21] Wong M, Staszewsky L, Latini R, Barlera S, Glazer R, Aknay N, Hester A, Anand I, Cohn JN. Severity of left ventricular remodeling defines outcomes and response to therapy in heart failure: Valsartan heart failure trial (Val-HeFT) echocardiographic data. J Am Coll Cardiol 2004;43:2022–7. [22] Chemla D, Castelain V, Herve P, Lecarpentier Y, Brimioulle S. Haemodynamic evaluation of pulmonary hypertension. Eur Respir J 2002;20:1314–31. [23] Guazzi M, Vicenzi M, Arena R, Guazzi MD. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study. Circ Heart Fail 2011;4: 8–17. [24] Lewis GD, Shah R, Shahzad K, Camuso JM, Pappagianopoulos PP, Hung J, Tawakol A, Gerszten RE, Systrom DM, Bloch KD, Semigran MJ. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation 2007;116: 1555–62. [25] Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, LeWinter MM, Rouleau JL, Bull DA, Mann DL, Deswal A, Stevenson LW, Givertz MM, Ofili EO, O’Connor CM, 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;309:1268–77.
Please cite this article in press as: Ibe T, et al. Pulmonary hypertension due to left heart disease: The prognostic implications of diastolic pulmonary vascular pressure gradient. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.07.015
JJCC-1136; No. of Pages 5 Journal of Cardiology xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Journal of Cardiology journal homepage: www.elsevier.com/locate/jjcc
Original article
Pulmonary hypertension due to left heart disease: The prognostic implications of diastolic pulmonary vascular pressure gradient Tatsuro Ibe (MD), Hiroshi Wada (MD, FJCC)*, Kenichi Sakakura (MD), Nahoko Ikeda (MD), Yoko Yamada (MD), Yoshitaka Sugawara (MD), Takeshi Mitsuhashi (MD, FJCC), Junya Ako (MD), Hideo Fujita (MD, FJCC), Shin-ichi Momomura (MD, FJCC) Division of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 April 2015 Received in revised form 18 July 2015 Accepted 23 July 2015 Available online xxx
Background: Compared to transpulmonary pressure gradient (TPPG), diastolic pulmonary vascular pressure gradient (DPG) may be a more sensitive and specific indicator for pulmonary hypertension (PH) due to left heart disease (LHD) with significant pulmonary vascular disease (PVD). The aim of this study was to investigate the incidence and clinical features of PH-LHD with PVD classified by DPG and TPPG. Methods: We analyzed 410 patients admitted for symptomatic heart failure (HF) (New York Heart Association 2) and who underwent right heart catheterization (RHC) at compensated stage between 2007 and 2012. Patients with PH-LHD were divided into 3 groups according to the value of DPG and TPPG (Non-PVD group: DPG 15 mmHg at rest were defined as PH-LHD. These patients were divided into 3 groups by DPG and TPPG. The definition of DPG was the difference between diastolic pulmonary artery pressure (dPAP) and PAWP (dPAP–PAWP), whereas the definition of TPPG was the difference between mPAP and PAWP (mPAP–PAWP). Three groups divided by the value of DPG and TPPG were as follows: (i) Non-PVD group: DPG 50 mm) Elevated BNP (>600 pg/ml)
1.89 3.57 1.49 0.98 0.17 1.83 1.50
0.77 1.33 0.75 0.18 0.04 0.24 0.72
to to to to to to to
p-value 4.64 9.55 2.99 5.32 0.65 14.2 3.15
0.17 0.01 0.26 0.98 0.01 0.57 0.28
PVD, pulmonary vascular disease; TPPG, transpulmonary pressure gradient; DPG, diastolic pulmonary vascular pressure gradient; mRAP, mean right atrial pressure; LV dysfunction, left ventricular dysfunction; LVDd, left ventricular diastolic dimension; LVDs, left ventricular systolic dimension; BNP, brain natriuretic peptide.
dimension was a better clinical indicator, which is usually considered as a worse clinical indicator [21]. However, in PH population, increased right ventricle (RV) afterload gradually results in RV dilation, and leftward septal shift [22]. It might be the reason why dilated LVDd was associated with better clinical outcomes in patients with PH-LHD. Previously, TPPG had been used as the definition of PH-LHD with PVD (reactive post-capillary PH), and some studies used this definition to evaluate the efficacy of pulmonary vasodilators for patients with PH-LHD. PDE-5 inhibitors such as sildenafil improved clinical status, exercise capacity, and cardiac function in HF patients [23,24], but they were not able to improve prognosis and rate of hospital readmission [25]. There might be the possibility of over- and underestimation about PH-LHD with PVD. Study limitations This is a retrospective and small sample study in a single tertiary center. The patients who were hospitalized in our center might be highly selected. The incidence and clinical features of the DPG-PVD group could vary depending on study patients. Therefore, the present study has an inherent patient selection bias. There is a possibility of incomplete follow-up because clinical follow-up was performed via office visit. Heart rhythm (sinus rhythm or not) might affect the measurements of RHC as well as echocardiography. Further prospective large-sample studies and dedicated pathological evaluation are warranted. Conclusions PH-LHD with PVD classified by DPG was significantly associated with poor long-term clinical outcomes, whereas the association between PH-LHD with PVD classified by TPPG and clinical outcomes did not reach statistical significance. However, further studies are needed, because there was no substantial difference in clinical outcomes between PH-LHD with PVD classified by DPG and PH-LHD with PVD classified by TPPG. Conflict of interest The authors declare that there is no conflict of interest. References [1] Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, Elliott CG, Gaine SP, Gladwin MT, Jing ZC, Krowka MJ, Langleben D, Nakanishi N, Souza R. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2009;54:S43–54.
5
[2] D’Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, Levy PS, Pietra GG, Reid LM, Reeves JT, Rich S, et al. Survival in patients with primary pulmonary hypertension, Results from a national prospective registry. Ann Intern Med 1991;115:343–9. [3] Matsubara H, Ogawa A. Treatment of idiopathic/hereditary pulmonary arterial hypertension. J Cardiol 2014;64:243–9. [4] Grigioni F, Potena L, Galie N, Fallani F, Bigliardi M, Coccolo F, Magnani G, Manes A, Barbieri A, Fucili A, Magelli C, Branzi A. Prognostic implications of serial assessments of pulmonary hypertension in severe chronic heart failure. J Heart Lung Transplant 2006;25:1241–6. [5] Tatebe S, Fukumoto Y, Sugimura K, Miyamichi-Yamamoto S, Aoki T, Miura Y, Nochioka K, Satoh K, Shimokawa H. Clinical significance of reactive postcapillary pulmonary hypertension in patients with left heart disease. Circ J 2012;76:1235–44. [6] Aronson D, Eitan A, Dragu R, Burger AJ. Relationship between reactive pulmonary hypertension and mortality in patients with acute decompensated heart failure. Circ Heart Fail 2011;4:644–50. [7] Naeije R, Vachiery JL, Yerly P, Vanderpool R. The transpulmonary pressure gradient for the diagnosis of pulmonary vascular disease. Eur Respir J 2013;41:217–23. [8] Shiba N, Watanabe J, Shinozaki T, Koseki Y, Sakuma M, Kagaya Y, Shirato K. Poor prognosis of Japanese patients with chronic heart failure following myocardial infarction – comparison with nonischemic cardiomyopathy. Circ J 2005;69:143–9. [9] Bonow RO, Lakatos E, Maron BJ, Epstein SE. Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventricular systolic function. Circulation 1991;84:1625–35. [10] Guglin M, Khan H. Pulmonary hypertension in heart failure. J Card Fail 2010;16:461–74. [11] Fang JC, DeMarco T, Givertz MM, Borlaug BA, Lewis GD, Rame JE, GombergMaitland M, Murali S, Frantz RP, McGlothlin D, Horn EM, Benza RL. 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;31:913–33. [12] Guazzi M, Borlaug BA. Pulmonary hypertension due to left heart disease. Circulation 2012;126:975–90. [13] Robbins IM, Newman JH, Johnson RF, Hemnes AR, Fremont RD, Piana RN, Zhao DX, Byrne DW. Association of the metabolic syndrome with pulmonary venous hypertension. Chest 2009;136:31–6. [14] Leung CC, Moondra V, Catherwood E, Andrus BW. Prevalence and risk factors of pulmonary hypertension in patients with elevated pulmonary venous pressure and preserved ejection fraction. Am J Cardiol 2010;106: 284–6. [15] 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;53:1119–26. [16] Bursi F, McNallan SM, Redfield MM, Nkomo VT, Lam CS, Weston SA, Jiang R, Roger VL. Pulmonary pressures and death in heart failure: a community study. J Am Coll Cardiol 2012;59:222–31. [17] Damy T, Goode KM, Kallvikbacka-Bennett A, Lewinter C, Hobkirk J, Nikitin NP, Dubois-Rande JL, Hittinger L, Clark AL, Cleland JG. Determinants and prognostic value of pulmonary arterial pressure in patients with chronic heart failure. Eur Heart J 2010;31:2280–90. [18] Lee JH, IM Cho K. Arterial stiffness, antiphospholipid antibodies, and pulmonary arterial hypertension in systemic lupus erythematosus. J Cardiol 2014;64:450–5. [19] Gerges C, Gerges M, Lang MB, Zhang Y, Jakowitsch J, Probst P, Maurer G, Lang IM. Diastolic pulmonary vascular pressure gradient: a predictor of prognosis in out-of-proportion pulmonary hypertension. Chest 2013;143:758–66. [20] Gheorghiade M, De Luca L, Fonarow GC, Filippatos G, Metra M, Francis GS. Pathophysiologic targets in the early phase of acute heart failure syndromes. Am J Cardiol 2005;96:11G–7G. [21] Wong M, Staszewsky L, Latini R, Barlera S, Glazer R, Aknay N, Hester A, Anand I, Cohn JN. Severity of left ventricular remodeling defines outcomes and response to therapy in heart failure: Valsartan heart failure trial (Val-HeFT) echocardiographic data. J Am Coll Cardiol 2004;43:2022–7. [22] Chemla D, Castelain V, Herve P, Lecarpentier Y, Brimioulle S. Haemodynamic evaluation of pulmonary hypertension. Eur Respir J 2002;20:1314–31. [23] Guazzi M, Vicenzi M, Arena R, Guazzi MD. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study. Circ Heart Fail 2011;4: 8–17. [24] Lewis GD, Shah R, Shahzad K, Camuso JM, Pappagianopoulos PP, Hung J, Tawakol A, Gerszten RE, Systrom DM, Bloch KD, Semigran MJ. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation 2007;116: 1555–62. [25] Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, LeWinter MM, Rouleau JL, Bull DA, Mann DL, Deswal A, Stevenson LW, Givertz MM, Ofili EO, O’Connor CM, 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;309:1268–77.
Please cite this article in press as: Ibe T, et al. Pulmonary hypertension due to left heart disease: The prognostic implications of diastolic pulmonary vascular pressure gradient. J Cardiol (2015), http://dx.doi.org/10.1016/j.jjcc.2015.07.015
