Evaluation and Management of Pulmonary Hypertension in Noncardiac Surgery: A Scientific Statement From the American Heart Association | Circulation
CTEPH Predictors Following Pulmonary Embolism
Risk for chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is associated with gender, delayed PE diagnosis, hypoxemia, heart load, D-dimer levels, and PE etiology. These findings were published in the Journal of the American Heart Association.
One of the most serious post-PE syndromes is CTEPH. A large variation in the rate of CTEPH has been reported and risk factors are not well understood.
The Contemporary Management and Outcomes in Patients With Venous Thromboembolism (COMMAND VTE) Registry-2 is a large cohort that recruited patients in Japan. In this study, patients (N=5197) with acute symptomatic venous thromboembolism between 2015 and 2020 at 31 sites were evaluated for CTEPH after acute PE (n=2787). The primary outcomes were the incidence of and risk factors for CTEPH.
Following a diagnosis of acute PE, the cumulative rates of CTEPH increased from 1.0% at 180 days to 1.7% at 1 year, 2.0% at 2 years, 2.3% at 3 years, and 2.4% at 4 and 5 years.
"
Several independent risk factors for CTEPH were identified, which could be useful for screening a high-risk population for CTEPH after acute PE.
The patients with (n=48) and without (n=2739) CTEPH comprised 77.1% and 56.3% women (P =.004), their mean ages were 65.2±15.0 and 66.6±15.4 years, and they had a BMI of 23.4±4.4 and 23.8±4.7, respectively.
At PE, patients who went on to develop CTEPH were more likely to have unprovoked PE (79.2% vs 40.2%; P <.001), to present with hypoxemia (70.8% vs 44.0%; P <.001), they had higher right heart load (91.7% vs 40.5%; P <.001), and they had lower D-dimer levels (median, 6.0 vs 11.4 mg/mL; P <.001) compared with patients who did not develop CTEPH.
Most patients with CTEPH (97.9%) were diagnosed within 3 years of PE. A total of 7 patients with CTEPH died, due to malignant diseases (n=4), infection (n=1), chronic obstructive pulmonary disease (n=1), and unknown reasons (n=1). The survival rates after CTEPH were 95.7%, 93.5%, 88.4%, 85.0%, 85.0%, and 72.9% at years 1 through 6, respectively.
Risk for CTEPH was associated with right heart load (adjusted hazard ratio [aHR], 9.28; 95% CI, 3.19-27.00; P <.001), unprovoked PE (aHR, 2.77; 95% CI, 1.22-6.30; P =.02), hypoxemia (aHR, 2.52; 95% CI, 1.26-5.04; P =.009), female gender (aHR, 2.09; 1.05-4.14; P =.04), per day delay in diagnosis from symptom onset (aHR, 1.04; 95% CI, 1.01-1.07; P =.01), and D-dimer levels per 1 mg/mL (aHR, 0.96; 95% CI, 0.92-0.99; P =.02).
This study was limited by the lack of diversity in the study cohort, which may limit the generalizability of these findings.
The study authors concluded, "In this large real-world VTE registry in the DOAC [direct oral anticoagulation] era, the cumulative detection of CTEPH after acute PE was 2.3% at 3 years. Several independent risk factors for CTEPH were identified, which could be useful for screening a high-risk population for CTEPH after acute PE."
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors' disclosures.
Pulmonary Arterial Hypertension: Current Therapeutic Strategies
Chin KM et al. (2005) The right ventricle in pulmonary hypertension. Coron Artery Dis 16: 13–18
Fishman AP (2004) Primary pulmonary arterial hypertension: a look back. J Am Coll Cardiol 43 (Suppl S): S2–S4
Galie N et al.; Task Force (2004) Guidelines on diagnosis and treatment of pulmonary arterial hypertension: the task force on diagnosis and treatment of pulmonary arterial hypertension of the European Society of Cardiology. Eur Heart J 25: 2243–2278
D'Alonzo GE et al. (1991) Survival in patients with primary pulmonary hypertension: results from a national prospective registry. Ann Intern Med 115: 343–349
Simonneau G et al. (2004) Clinical classification of pulmonary hypertension. J Am Coll Cardiol 43 (Suppl S): S5–S12
Loyd JE et al. (1988) Heterogeneity of pathologic lesions in familial primary pulmonary hypertension. Am Rev Respir Dis 138: 952–957
Machado RD et al. (2001) BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am J Hum Genet 68: 92–102
Thomson J et al. (2001) Familial and sporadic primary pulmonary hypertension is caused by BMPR2 gene mutations resulting in haploinsufficiency of the bone morphogenetic protein type II receptor [Abstract]. J Heart Lung Transplant 20: a149
Bobik A (2006) Transforming growth factor-betas and vascular disorders. Arterioscler Thromb Vasc Biol 26: 1712–1720
Machado RD et al. (2006) Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension. Hum Mutat 27: 121–132
Elliott CG et al. (2006) Relationship of BMPR2 mutations to vasoreactivity in pulmonary arterial hypertension. Circulation 113: 2509–2515
Christman BW et al. (1992) An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med 327: 70–75
Giaid A and Saleh D (1995) Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 333: 214–221
Giaid A et al. (1993) Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 328: 1732–1739
Humbert M et al. (2004) Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 43 (Suppl S): S13–S24
Galie N et al. (2004) Comparative analysis of clinical trials and evidence-based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol 43 (Suppl S): S81–S88
Olschewski H et al. (2002) Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 347: 322–329
Seyfarth HJ et al. (online 11 May 2006) Long-term bosentan in chronic thromboembolic pulmonary hypertension [http://content.Karger.Com/ProdukteDB/produkte.Asp?Aktion=ShowAbstract&ArtikelNr=93322&Ausgabe=0&ProduktNr=224278] (accessed 19 March 2007)
Ahmadi-Simab K et al. (2006) Bosentan for severe pulmonary arterial hypertension related to systemic sclerosis with interstitial lung disease. Eur J Clin Invest 36 (Suppl 3): S44–S48
Madden BP et al. (2006) A potential role for sildenafil in the management of pulmonary hypertension in patients with parenchymal lung disease. Vascul Pharmacol 44: 372–376
Barst RJ (1986) Pharmacologically induced pulmonary vasodilatation in children and young adults with primary pulmonary hypertension. Chest 89: 497–503
Pepke-Zaba J et al. (1991) Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet 338: 1173–1174
Rubin LJ et al. (1982) Prostacyclin-induced acute pulmonary vasodilation in primary pulmonary hypertension. Circulation 66: 334–338
Morgan JM et al. (1991) Adenosine as a vasodilator in primary pulmonary hypertension. Circulation 84: 1145–1149
Sitbon O et al. (2005) Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 111: 3105–3111
Rich S et al. (1992) The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. N Engl J Med 327: 76–81
Woodmansey PA et al. (1996) Acute pulmonary vasodilatory properties of amlodipine in humans with pulmonary hypertension. Heart 75: 171–173
Franz IW et al. (2002) The effect of amlodipine on exercise-induced pulmonary hypertension and right heart function in patients with chronic obstructive pulmonary disease. Z Kardiol 91: 833–839
Fuster V et al. (1984) Primary pulmonary hypertension: natural history and the importance of thrombosis. Circulation 70: 580–587
Robbins IM et al. (2006) A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension. Eur Respir J 27: 578–584
Veyssier-Belot C et al. (1999) Role of endothelial and smooth muscle cells in the physiopathology and treatment management of pulmonary hypertension. Cardiovasc Res 44: 274–282
Barst RJ et al. (1996) A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension: the Primary Pulmonary Hypertension Study Group. N Engl J Med 334: 296–302
McLaughlin VV et al. (2002) Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation 106: 1477–1482
Sitbon O et al. (2002) Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol 40: 780–788
Simonneau G et al.; Treprostinil Study Group (2002) Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 165: 800–804
McLaughlin VV et al.; Treprostinil Study Group (2003) Efficacy and safety of treprostinil: an epoprostenol analog for primary pulmonary hypertension. J Cardiovasc Pharmacol 41: 293–299
Gomberg-Maitland M et al. (2005) Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension. Am J Respir Crit Care Med 172: 1586–1589
Tapson VF et al. (2006) Safety and efficacy of IV treprostinil for pulmonary arterial hypertension: a prospective, multicenter, open-label, 12-week trial. Chest 129: 683–688
Hoeper MM et al. (2000) A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension: German PPH study group. J Am Coll Cardiol 35: 176–182
Hoeper MM et al. (2000) Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med 342: 1866–1870
Nagaya N et al. (1999) Effect of orally active prostacyclin analogue on survival of outpatients with primary pulmonary hypertension. J Am Coll Cardiol 34: 1188–1192
Galie N et al.; Arterial Pulmonary Hypertension and Beraprost European (ALPHABET) Study Group (2002) Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol 39: 1496–1502
Barst RJ et al.; Beraprost Study Group (2003) Beraprost therapy for pulmonary arterial hypertension. J Am Coll Cardiol 41: 2119–2125
Cacoub P et al. (1993) Endothelin-1 in primary pulmonary hypertension and the Eisenmenger syndrome. Am J Cardiol 71: 448–450
Kedzierski RM et al. (2001) Endothelin system: the double-edged sword in health and disease. Annu Rev Pharmacol Toxicol 41: 851–876
Rubin LJ et al. (2002) Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 346: 896–903
Galie N et al. (2004) The endothelin system in pulmonary arterial hypertension. Cardiovasc Res 61: 227–237
Galie N et al. (2003) Effects of the oral endothelin-receptor antagonist bosentan on echocardiographic and doppler measures in patients with pulmonary arterial hypertension. J Am Coll Cardiol 41: 1380–1386
Channick R et al. (2001) Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary hypertension: a placebo-controlled study. J Heart Lung Transplant 20: 262–263
Barst RJ et al. (2004) Sitaxsentan therapy for pulmonary arterial hypertension. Am J Respir Crit Care Med 169: 441–447
Barst RJ et al. (2006) Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan. J Am Coll Cardiol 47: 2049–2056
Billman GE (2002) Ambrisentan (Myogen). Curr Opin Investig Drugs 3: 1483–1486
Galie N et al. (2005) Ambrisentan therapy for pulmonary arterial hypertension. J Am Coll Cardiol 46: 529–535
Tantini B et al. (2005) Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells. Basic Res Cardiol 100: 131–138
Prasad S et al. (2000) Sildenafil in primary pulmonary hypertension. N Engl J Med 343: 1342
Bhatia S et al. (2003) Immediate and long-term hemodynamic and clinical effects of sildenafil in patients with pulmonary arterial hypertension receiving vasodilator therapy. Mayo Clin Proc 78: 1207–1213
Michelakis ED et al. (2003) Long-term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertension. Circulation 108: 2066–2069
Sastry BK et al. (2004) Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized, placebo-controlled, double-blind, crossover study. J Am Coll Cardiol 43: 1149–1153
Galie N et al. (2005) Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 353: 2148–2157
Affuso F et al. (2006) Tadalafil improves quality of life and exercise tolerance in idiopathic pulmonary arterial hypertension. Int J Cardiol 108: 429–431
Nagaoka T et al. (2006) Involvement of RhoA/Rho kinase signaling in pulmonary hypertension of the fawn-hooded rat. J Appl Physiol 100: 996–1002
Abe K et al. (2004) Long-term treatment with a Rho-kinase inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats. Circ Res 94: 385–393
Ishikura K et al. (2006) Beneficial acute effects of rho-kinase inhibitor in patients with pulmonary arterial hypertension. Circ J 70: 174–178
Guilluy C et al. (2005) Inhibition of RhoA/Rho kinase pathway is involved in the beneficial effect of sildenafil on pulmonary hypertension. Br J Pharmacol 146: 1010–1018
Barst RJ (2005) PDGF signaling in pulmonary arterial hypertension. J Clin Invest 115: 2691–2694
Dingli D et al. (2001) Unexplained pulmonary hypertension in chronic myeloproliferative disorders. Chest 120: 801–808
Hoffman R et al. (2006) Is bone marrow fibrosis the real problem? Blood 107: 3421–3422
Schermuly RT et al. (2005) Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 115: 2811–2821
Ghofrani HA et al. (2005) Imatinib for the treatment of pulmonary arterial hypertension. N Engl J Med 353: 1412–1413
Souza R et al. (2006) Long term imatinib treatment in pulmonary arterial hypertension. Thorax 61: 736
Patterson KC et al. (2006) Imatinib mesylate in the treatment of refractory idiopathic pulmonary arterial hypertension. Ann Intern Med 145: 152–153
Kerkela R et al. (2006) Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med 12: 908–916
Hu H et al. (2006) Simvastatin enhances bone morphogenetic protein receptor type II expression. Biochem Biophys Res Commun 339: 59–64
Taraseviciene-Stewart L et al. (2006) Simvastatin causes endothelial cell apoptosis and attenuates severe pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 291: L668–L676
Kao PN (2005) Simvastatin treatment of pulmonary hypertension: an observational case series. Chest 127: 1446–1452
Henriques-Coelho T et al. (2006) Ghrelin reverses molecular, structural and hemodynamic alterations of the right ventricle in pulmonary hypertension. Rev Port Cardiol 25: 55–63
Taraseviciene-Stewart L et al. (2005) Treatment of severe pulmonary hypertension: a bradykinin receptor 2 agonist B9972 causes reduction of pulmonary artery pressure and right ventricular hypertrophy. Peptides 26: 1292–300
Marcos E et al. (2004) Serotonin-induced smooth muscle hyperplasia in various forms of human pulmonary hypertension. Circ Res 94: 1263–1270
Cogolludo A et al. (2006) Serotonin inhibits voltage-gated K+ currents in pulmonary artery smooth muscle cells: role of 5-HT2A receptors, caveolin-1, and Kv1.5 channel internalization. Circ Res 98: 931–938
Guignabert C et al. (2005) Serotonin transporter inhibition prevents and reverses monocrotaline-induced pulmonary hypertension in rats. Circulation 111: 2812–2819
Petkov V et al. (2006) The vasoactive intestinal peptide receptor turnover in pulmonary arteries indicates an important role for VIP in the rat lung circulation. Ann NY Acad Sci 1070: 481–483
Petkov V et al. (2003) Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J Clin Invest 111: 1339–1346
Michelakis ED et al. (2003) The NO− K+ channel axis in pulmonary arterial hypertension. Activation by experimental oral therapies. Adv Exp Med Biol 543: 293–322
Maurey C et al. (2006) Interaction of KATP channels and endothelin-1 in lambs with persistent pulmonary hypertension of the newborn. Pediatr Res 60: 252–257
Pozeg ZI et al. (2003) In vivo gene transfer of the O2-sensitive potassium channel Kv1.5 reduces pulmonary hypertension and restores hypoxic pulmonary vasoconstriction in chronically hypoxic rats. Circulation 107: 2037–2044
McMurtry MS et al. (2004) Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ Res 95: 830–840
Wong PS et al. (2001) Primary pulmonary hypertension in pregnancy. JR Soc Med 94: 523–525
Rich S et al. (1998) The short-term effects of digoxin in patients with right ventricular dysfunction from pulmonary hypertension. Chest 114: 787–792
Naeije R and Vachiery JL (2001) Medical therapy of pulmonary hypertension: conventional therapies. Clin Chest Med 22: 517–527
Radley-Smith R et al. (2006) Transplantation as a treatment for end-stage pulmonary hypertension in childhood. Paediatr Respir Rev 7: 117–122
Habashi JP et al. (2006) Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 312: 117–121
Nakamoto T et al. (2005) Effects of olmesartan medoxomil as an angiotensin II-receptor blocker in chronic hypoxic rats. Eur J Pharmacol 528: 43–51
Humbert M et al. (2004) Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J 24: 353–359
Hoeper MM et al. (2006) Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur Respir J 28: 691–694
Seyfarth HJ et al. (2005) Bosentan improves exercise tolerance and Tei index in patients with pulmonary hypertension and prostanoid therapy. Chest 128: 709–713
McLaughlin VV et al. (2006) Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am J Respir Crit Care Med 174: 1257–1263
Gomberg-Maitland M (2006) Learning to pair therapies and the expanding matrix for pulmonary arterial hypertension: is more better? Eur Respir J 28: 683–686
Wilkens H et al. (2001) Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation 104: 1218–1222
Gomberg-Maitland M et al. (2005) Efficacy and safety of sildenafil added to treprostinil in pulmonary hypertension. Am J Cardiol 96: 1334–1336
Clozel M et al. (2006) Bosentan, sildenafil, and their combination in the monocrotaline model of pulmonary hypertension in rats. Exp Biol Med (Maywood) 231: 967–973
Hoeper MM et al. (2004) Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension. Eur Respir J 24: 1007–1010
Morice AH et al. (2005) Combination therapy with bosentan and phosphodiesterase-5 inhibitor in pulmonary arterial hypertension. Eur Respir J 26: 180
Comments
Post a Comment