Pulmonary hypertension in adults with congenital heart disease
- Heidi M Connolly, MD, FASE
Heidi M Connolly, MD, FASE
- Section Editor — Congenital Heart Disease
- Professor of Medicine
- Mayo Medical School
- Robert P Frantz, MD
Robert P Frantz, MD
- Professor of Medicine
- Mayo Clinic College of Medicine
- Section Editors
- Candice Silversides, MD, MS, FRCPC
Candice Silversides, MD, MS, FRCPC
- Section Editor — Congenital Heart Disease
- Associate Professor of Medicine
- University of Toronto
- Jess Mandel, MD
Jess Mandel, MD
- Section Editor — Pulmonary Vascular Disease
- Professor of Medicine
- University of California, San Diego
Approximately 3 to 10 percent of patients with congenital heart disease (CHD) develop pulmonary arterial hypertension (henceforth described as pulmonary hypertension – congenital heart disease [PH-CHD]) [1,2]. Early diagnosis and repair of CHD has decreased the number of patients with Eisenmenger syndrome; however, the overall number of PH-CHD patients is increasing because more patients with complex and palliated CHD survive to adulthood . PH-CHD is more common in women, patients with shunt lesions, and older CHD patients, and is associated with excess mortality and increase in healthcare costs .
The clinical manifestations, diagnosis, and management of PH-CHD in adults are discussed here. The evaluation and prognosis of Eisenmenger syndrome are discussed separately. (See "Evaluation and prognosis of Eisenmenger syndrome" and "Management of Eisenmenger syndrome".)
Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure ≥25 mmHg at rest. PH can be secondary to elevated pulmonary venous pressure (post-capillary pulmonary hypertension), elevated pulmonary vascular resistance (PVR), defined by PVR >3 Wood units (precapillary PH), or combination of the two (mixed PH). PH-congenital heart disease (PH-CHD) can also be secondary to increased flow through the pulmonary vasculature; this type of PH is not typically observed in non-CHD populations, aside from high output states such as severe anemia, thyrotoxicosis, cirrhosis, and large dialysis fistulae. (See "Classification and prognosis of pulmonary hypertension in adults".)
Patients with pulmonary hypertension – congenital heart disease (PH-CHD) represent a heterogeneous patient population, predominantly in group 1 (precapillary or pulmonary arterial hypertension [PAH]) PH clinical classification  (table 1). (See "Clinical features and diagnosis of pulmonary hypertension in adults", section on 'Diagnostic criteria'.)
In the past, a classification system based on cause of PH-CHD was used and patients were classified into the following groups:
- Lowe BS, Therrien J, Ionescu-Ittu R, et al. Diagnosis of pulmonary hypertension in the congenital heart disease adult population impact on outcomes. J Am Coll Cardiol 2011; 58:538.
- van Riel AC, Schuuring MJ, van Hessen ID, et al. Contemporary prevalence of pulmonary arterial hypertension in adult congenital heart disease following the updated clinical classification. Int J Cardiol 2014; 174:299.
- Marelli AJ, Mackie AS, Ionescu-Ittu R, et al. Congenital heart disease in the general population: changing prevalence and age distribution. Circulation 2007; 115:163.
- McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation 2009; 119:2250.
- Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013; 62:D34.
- Miller VM, Aarhus LL, Vanhoutte PM. Modulation of endothelium-dependent responses by chronic alterations of blood flow. Am J Physiol 1986; 251:H520.
- Hopkins WE. The remarkable right ventricle of patients with Eisenmenger syndrome. Coron Artery Dis 2005; 16:19.
- Hopkins WE, Waggoner AD. Severe pulmonary hypertension without right ventricular failure: the unique hearts of patients with Eisenmenger syndrome. Am J Cardiol 2002; 89:34.
- Yoshibayashi M, Nishioka K, Nakao K, et al. Plasma endothelin concentrations in patients with pulmonary hypertension associated with congenital heart defects. Evidence for increased production of endothelin in pulmonary circulation. Circulation 1991; 84:2280.
- Ishikawa S, Miyauchi T, Sakai S, et al. Elevated levels of plasma endothelin-1 in young patients with pulmonary hypertension caused by congenital heart disease are decreased after successful surgical repair. J Thorac Cardiovasc Surg 1995; 110:271.
- Fuse S, Kamiya T. Plasma thromboxane B2 concentration in pulmonary hypertension associated with congenital heart disease. Circulation 1994; 90:2952.
- Kaemmerer H, Fratz S, Braun SL, et al. Erythrocyte indexes, iron metabolism, and hyperhomocysteinemia in adults with cyanotic congenital cardiac disease. Am J Cardiol 2004; 94:825.
- Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 Guidelines for the Management of Adults with Congenital Heart Disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to develop guidelines on the management of adults with congenital heart disease). Circulation 2008; 118:e714.
- Opotowsky AR. Clinical evaluation and management of pulmonary hypertension in the adult with congenital heart disease. Circulation 2015; 131:200.
- Fenstad ER, Le RJ, Sinak LJ, et al. Pericardial effusions in pulmonary arterial hypertension: characteristics, prognosis, and role of drainage. Chest 2013; 144:1530.
- Opotowsky AR, Ojeda J, Rogers F, et al. A simple echocardiographic prediction rule for hemodynamics in pulmonary hypertension. Circ Cardiovasc Imaging 2012; 5:765.
- Abbas AE, Franey LM, Marwick T, et al. Noninvasive assessment of pulmonary vascular resistance by Doppler echocardiography. J Am Soc Echocardiogr 2013; 26:1170.
- Lee MS, Oyama J, Bhatia R, et al. Left main coronary artery compression from pulmonary artery enlargement due to pulmonary hypertension: a contemporary review and argument for percutaneous revascularization. Catheter Cardiovasc Interv 2010; 76:543.
- Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease). Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2008; 52:e143.
- Tunariu N, Gibbs SJ, Win Z, et al. Ventilation-perfusion scintigraphy is more sensitive than multidetector CTPA in detecting chronic thromboembolic pulmonary disease as a treatable cause of pulmonary hypertension. J Nucl Med 2007; 48:680.
- Atz AM, Zak V, Mahony L, et al. Survival data and predictors of functional outcome an average of 15 years after the Fontan procedure: the pediatric heart network Fontan cohort. Congenit Heart Dis 2015; 10:E30.
- Giannakoulas G, Mouratoglou SA, Gatzoulis MA, Karvounis H. Blood biomarkers and their potential role in pulmonary arterial hypertension associated with congenital heart disease. a systematic review. Int J Cardiol 2014; 174:618.
- Galie N, Humbert M, Vachiery JL, 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 2015; :[Epub before print].
- Diller GP, Gatzoulis MA. Pulmonary vascular disease in adults with congenital heart disease. Circulation 2007; 115:1039.
- Sandoval J, Aguirre JS, Pulido T, et al. Nocturnal oxygen therapy in patients with the Eisenmenger syndrome. Am J Respir Crit Care Med 2001; 164:1682.
- Grocott MP, Martin DS, Levett DZ, et al. Arterial blood gases and oxygen content in climbers on Mount Everest. N Engl J Med 2009; 360:140.
- Wilkins MR, Ghofrani HA, Weissmann N, et al. Pathophysiology and treatment of high-altitude pulmonary vascular disease. Circulation 2015; 131:582.
- Broberg CS, Ujita M, Prasad S, et al. Pulmonary arterial thrombosis in eisenmenger syndrome is associated with biventricular dysfunction and decreased pulmonary flow velocity. J Am Coll Cardiol 2007; 50:634.
- Ammash N, Warnes CA. Cerebrovascular events in adult patients with cyanotic congenital heart disease. J Am Coll Cardiol 1996; 28:768.
- Beghetti M, Galiè N. Eisenmenger syndrome a clinical perspective in a new therapeutic era of pulmonary arterial hypertension. J Am Coll Cardiol 2009; 53:733.
- Iversen K, Jensen AS, Jensen TV, et al. Combination therapy with bosentan and sildenafil in Eisenmenger syndrome: a randomized, placebo-controlled, double-blinded trial. Eur Heart J 2010; 31:1124.
- Rosenkranz S, Ghofrani HA, Beghetti M, et al. Riociguat for pulmonary arterial hypertension associated with congenital heart disease. Heart 2015; 101:1792.
- Sitbon O, Channick R, Chin KM, et al. Selexipag for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med 2015; 373:2522.
- Simonneau G, Barst RJ, Galie N, et al. 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 2002; 165:800.
- Rosenzweig EB, Kerstein D, Barst RJ. Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects. Circulation 1999; 99:1858.
- Moller JH, Patton C, Varco RL, Lillehei CW. Late results (30 to 35 years) after operative closure of isolated ventricular septal defect from 1954 to 1960. Am J Cardiol 1991; 68:1491.
- van Albada ME, Berger RM. Pulmonary arterial hypertension in congenital cardiac disease--the need for refinement of the Evian-Venice classification. Cardiol Young 2008; 18:10.
- Schulze-Neick I, Beghetti M. Classifying pulmonary hypertension in the setting of the congenitally malformed heart--cleaning up a dog's dinner. Cardiol Young 2008; 18:22.
- Lopes AA, O'Leary PW. Measurement, interpretation and use of hemodynamic parameters. Cardiol Young 2009; 19 Suppl 1:8.
- Galie N, Manes A, Palazzini M, et al. Management of pulmonary arterial hypertension associated with congenital systemic-to-pulmonary shunts and Eisenmenger's syndrome. Drugs 2008; 68:1049.
- Sandoval J, Gomez-Arroyo J, Gaspar J, Pulido-Zamudio T. Interventional and surgical therapeutic strategies for pulmonary arterial hypertension: Beyond palliative treatments. J Cardiol 2015; 66:304.
- Adriaenssens T, Delcroix M, Van Deyk K, Budts W. Advanced therapy may delay the need for transplantation in patients with the Eisenmenger syndrome. Eur Heart J 2006; 27:1472.
- Bédard E, Dimopoulos K, Gatzoulis MA. Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension? Eur Heart J 2009; 30:256.
- Elkayam U, Gleicher N. Cardiac problems in pregnancy. I. Maternal aspects: the approach to the pregnant patient with heart disease. JAMA 1984; 251:2838.
- Hankins GD, Berryman GK, Scott RT Jr, Hood D. Maternal arterial desaturation with 15-methyl prostaglandin F2 alpha for uterine atony. Obstet Gynecol 1988; 72:367.
- Kiely DG, Condliffe R, Webster V, et al. Improved survival in pregnancy and pulmonary hypertension using a multiprofessional approach. BJOG 2010; 117:565.
- Jaïs X, Olsson KM, Barbera JA, et al. Pregnancy outcomes in pulmonary arterial hypertension in the modern management era. Eur Respir J 2012; 40:881.
- McLaughlin VV, Shah SJ, Souza R, Humbert M. Management of pulmonary arterial hypertension. J Am Coll Cardiol 2015; 65:1976.
- Bonnin M, Mercier FJ, Sitbon O, et al. Severe pulmonary hypertension during pregnancy: mode of delivery and anesthetic management of 15 consecutive cases. Anesthesiology 2005; 102:1133.
- Vongpatanasin W, Brickner ME, Hillis LD, Lange RA. The Eisenmenger syndrome in adults. Ann Intern Med 1998; 128:745.
- Kelion AD, Webb TP, Gardner MA, et al. The warm-up effect protects against ischemic left ventricular dysfunction in patients with angina. J Am Coll Cardiol 2001; 37:705.
- Van Hare GF, Ackerman MJ, Evangelista JA, et al. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 4: Congenital Heart Disease: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2372.
- Verheugt CL, Uiterwaal CS, van der Velde ET, et al. Mortality in adult congenital heart disease. Eur Heart J 2010; 31:1220.
- Manes A, Palazzini M, Leci E, et al. Current era survival of patients with pulmonary arterial hypertension associated with congenital heart disease: a comparison between clinical subgroups. Eur Heart J 2014; 35:716.
- CLINICAL MANIFESTATIONS
- Symptoms and signs
- Initial test findings
- - Laboratory tests
- - Electrocardiogram
- - Chest radiograph
- DIAGNOSIS AND EVALUATION
- When to suspect pulmonary hypertension-congenital heart disease
- Approach to diagnosis and evaluation
- Key diagnostic tests
- - Cardiovascular imaging
- Computed tomography or cardiovascular magnetic resonance
- - Cardiac catheterization
- - Nuclear lung scintigraphy
- - Pulmonary function tests with volumes and diffusion capacity
- Tests to evaluate patients with PH-CHD
- - Natriuretic peptide level
- - Pulse oximetry
- - Exercise test
- DIFFERENTIAL DIAGNOSIS
- General management
- Disease-specific therapy
- - Primary therapy
- - Advanced therapy
- Patient selection
- Agent selection
- Interventional treatments including cardiac surgery
- Management of pregnancy
- Participation in athletics
- SUMMARY AND RECOMMENDATIONS