Abstract
Eisenmenger syndrome is the most severe and extreme phenotype of pulmonary arterial
hypertension associated with congenital heart disease. A large nonrestrictive systemic
left-to-right shunt triggers the development of pulmonary vascular disease, progressive
pulmonary arterial hypertension, and increasing pulmonary vascular resistance at the
systemic level, which ultimately results in shunt reversal. Herein, we review the
changing epidemiological patterns and pathophysiology of Eisenmenger syndrome. Multiorgan
disease is an integral manifestation of Eisenmenger syndrome and includes involvement
of the cardiac, hematological, neurological, respiratory, gastrointestinal, urinary,
immunological, musculoskeletal, and endocrinological systems. Standardized practical
guidelines for the assessment, management, risk stratification, and follow-up of this
very fragile and vulnerable population are discussed. Multidisciplinary care is the
best clinical practice. An approach to the prevention and management of a broad spectrum
of complications is provided. Relevant therapeutic questions are discussed, including
anticoagulation, noncardiac surgery, physical activity, transplantation, and advanced-care
planning (palliative care). Advanced pulmonary arterial hypertension therapies are
indicated in patients with Eisenmenger syndrome and World Health Organization functional
class II or higher symptoms to improve functional capacity, quality of life, and—less
well documented—survival. Specific recommendations regarding monotherapy or combination
therapy are provided according to functional class and clinical response. The ultimate
challenge for all care providers remains early detection and management of intracardiac
and extracardiac shunts, considering that Eisenmenger syndrome is a preventable condition.
Résumé
Le syndrome d'Eisenmenger est le phénotype le plus sévère et extrême de l'hypertension
artérielle pulmonaire associée aux cardiopathies congénitales. Un important shunt
gauche-droit systémique non restrictif engendre une maladie vasculaire pulmonaire,
l'apparition d'une hypertension artérielle pulmonaire et la majoration des résistances
vasculaires pulmonaires; les pressions pulmonaires atteignent un seuil systémique
à l'origine du renversement du shunt. Cet article discute des bases physiopathologiques
et du changement épidémiologique du syndrome d'Eisenmenger. L'atteinte multiviscérale
est caractéristique du syndrome d'Eisenmenger impliquant le système cardio-vasculaire,
hématologique, neurologique, respiratoire, gastro-intestinal, urinaire, immunologique,
musculo-squelettique et endocrinien. Nous proposons des lignes directrices pratiques
pour l’évaluation, la prise en charge, la stratification des risques et le suivi de
cette population fragile et vulnérable. Les pratiques cliniques exemplaires recommandent
des soins multidisciplinaires. Nous présentons aussi une approche pour la prévention
et la prise en charge d'un grand éventail de complications et nous abordons des questions
thérapeutiques pertinentes, notamment l'anticoagulothérapie, la chirurgie non cardiaque,
l'activité physique, la greffe et la planification préalable des soins (soins palliatifs).
Les traitements spécifiques de l'hypertension artérielle pulmonaire sont indiqués
chez les patients atteints de syndrome d'Eisenmenger avec une classe fonctionnelle
de II ou plus de l'Organisation mondiale de la Santé afin d'améliorer la capacité
fonctionnelle, la qualité de vie, et bien que moins documentée la survie. Enfin, nous
formulons des recommandations spécifiques concernant le recours à la monothérapie
ou à l'association thérapeutique selon la classe fonctionnelle et la réponse clinique.
Le diagnostic précoce et la prise en charge optimale des shunts intracardiaques et
extracardiaques sont les défis ultimes des équipes traitantes médicales pour prévenir
le syndrome d'Eisenmenger.
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References
- The Eisenmenger syndrome or pulmonary hypertension with reversed central shunt: I.Br Med J. 1958; 2: 701-709
- The Eisenmenger syndrome or pulmonary hypertension with reversed central shunt.Br Med J. 1958; 2: 755-762
- 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: 67-119
- An overview of the 6th World Symposium on Pulmonary Hypertension.Eur Respir J. 2019; 53
- Die angeborenen Defecte der Kammerscheidewand des Herzens.Z Klin Med. 1897; 32: 1-28
- The spectrum of adult congenital heart disease in Europe: morbidity and mortality in a 5 year follow-up period: the Euro Heart Survey on adult congenital heart disease.Eur Heart J. 2005; 26: 2325-2333
- Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a Dutch registry.Int J Cardiol. 2007; 120: 198-204
- Pulmonary arterial hypertension in adult congenital heart disease.Heart. 2018; 104: 1568-1574
- Eisenmenger syndrome and long-term survival in patients with Down syndrome and congenital heart disease.Heart. 2016; 102: 1552-1557
- The pathology of hypertensive pulmonary vascular disease; a description of six grades of structural changes in the pulmonary arteries with special reference to congenital cardiac septal defects.Circulation. 1958; 18: 533-547
- Lung biopsy in congenital heart disease: a morphometric approach to pulmonary vascular disease.Circulation. 1978; 58: 1107-1122
- Pulmonary vascular disease in infants with complete atrioventricular septal defect.Int J Cardiol. 1987; 15: 91-103
- BMPR2 mutations in pulmonary arterial hypertension with congenital heart disease.Eur Respir J. 2004; 24: 371-374
- Carotid chemoreceptor "resetting" revisited.Respir Physiol Neurobiol. 2013; 185: 30-43
- The adult patient with Eisenmenger syndrome: a medical update after Dana Point Part III: specific management and surgical aspects.Curr Cardiol Rev. 2010; 6: 363-372
- Hematological management of the cyanotic adult with congenital heart disease.Int J Cardiol. 2004; 97: 109-115
- Management of adults with cyanotic congenital heart disease.Heart. 2015; 101: 485-494
- Risk and resiliency: thrombotic and ischemic vascular events, in cyanotic congenital heart disease.Heart. 2015; 101: 1521-1522
- Blood viscosity and its relationship to iron deficiency, symptoms, and exercise capacity in adults with cyanotic congenital heart disease.J Am Coll Cardiol. 2006; 48: 356-365
- Replacement therapy for iron deficiency improves exercise capacity and qualtiy of life in patients with cyanotic cogential heart disease and/or the Eisenmenger syndrome.Int J Cardiol. 2011; 151: 307-312
- Seeking optimal relation between oxygen saturation and hemoglobin concentration in adults with cyanosis from congenital heart disease.Am J Cardiol. 2011; 107: 595-599
- Systemic endothelial dysfunction in adults with cyanotic congenital heart disease.Circulation. 2005; 112: 1106-1112
- Cerebrovascular events in adult patients with cyanotic congenital heart disease.J Am Coll Cardiol. 1996; 28: 768-772
- Risk of stroke in adults with cyanotic congenital heart disease.Circulation. 1993; 87: 1954-1959
- Echocardiographic screening for pulmonary hypertension in congenital heart disease: JACC Review Topic of the Week.J Am Coll Cardiol. 2018; 72: 2778-2788
- Responsiveness to inhaled nitric oxide is a predictor for mid-term survival in adult patients with congenital heart defects and pulmonary arterial hypertension.Eur Heart J. 2004; 25: 1651-1656
- The remarkable right ventricle of patients with Eisenmenger syndrome.Coron Artery Dis. 2005; 16: 19-25
- Model of chronic adaptation: right ventricular function in Eisenmenger syndrome.Eur Heart J. 2007; 9: H54-H60
- Survival prospects of treatment naive patients with Eisenmenger: a systematic review of the literature and report of own experience.Heart. 2014; 100: 1366-1372
- Exercise performance and quality of life is more impaired in Eisenmenger syndrome than in complex cyanotic congenital heart disease with pulmonary stenosis.Int J Cardiol. 2011; 150: 177-181
- Past and current cause-specific mortality in Eisenmenger syndrome.Eur Heart J. 2017; 38: 2060-2067
- Worsening in oxygen saturation and exercise capacity predict adverse outcome in patients with Eisenmenger syndrome.Int J Cardiol. 2013; 168: 1386-1392
- Six-minute walk test distance and resting oxygen saturations but not functional class predict outcome in adult patients with Eisenmenger syndrome.Int J Cardiol. 2013; 168: 4784-4789
- Predictors of death in contemporary adult patients with Eisenmenger syndrome: a multicenter study.Circulation. 2017; 135: 1432-1440
- Physiological differences between various types of Eisenmenger syndrome and relation to outcome.Int J Cardiol. 2015; 179: 455-460
- Determinants of survival and length of survival in adults with Eisenmenger syndrome.Am J Cardiol. 1999; 84: 677-681
- Eisenmenger syndrome in adults: ventricular septal defect, truncus arteriosus, univentricular heart.J Am Coll Cardiol. 1999; 34: 223-232
- Eisenmenger syndrome: factors relating to deterioration and death.Eur Heart J. 1998; 19: 1845-1855
- Pulmonary thrombosis in adults with Eisenmenger syndrome.J Am Coll Cardiol. 2003; 42: 1982-1987
- Proximal pulmonary arterial and intrapulmonary radiologic features of Eisenmenger syndrome and primary pulmonary hypertension.Am J Cardiol. 2003; 92: 182-187
- Pulmonary arterial thrombosis in eisenmenger syndrome is associated with biventricular dysfunction and decreased pulmonary flow velocity.J Am Coll Cardiol. 2007; 50: 634-642
- Does anticoagulation in Eisenmenger syndrome impact long-term survival?.Congenit Heart Dis. 2012; 7: 268-276
- Current therapy and outcome of Eisenmenger syndrome: data of the German National Register for congenital heart defects.Eur Heart J. 2016; 37: 1449-1455
- Right and left ventricular dysfunction in patients with severe pulmonary disease.Chest. 1998; 113: 576-583
- Outcome of adults with Eisenmenger syndrome treated with drugs specific to pulmonary arterial hypertension: a French multicentre study.Arch Cardiovasc Dis. 2017; 110: 303-316
- Pulmonary vasodilator therapy is associated with greater survival in Eisenmenger syndrome.Heart. 2018; 104: 732-737
- Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study.Circulation. 2006; 114: 48-54
- Longer-term bosentan therapy improves functional capacity in Eisenmenger syndrome: results of the BREATHE-5 open-label extension study.Int J Cardiol. 2008; 127: 27-32
- Atrial septal defects versus ventricular septal defects in BREATHE-5, a placebo-controlled study of pulmonary arterial hypertension related to Eisenmenger's syndrome: a subgroup analysis.Int J Cardiol. 2010; 144: 373-378
- Long-term safety, tolerability and efficacy of bosentan in adults with pulmonary arterial hypertension associated with congenital heart disease.Heart. 2007; 93: 974-976
- Prolonged beneficial effect of bosentan treatment and 4-year survival rates in adult patients with pulmonary arterial hypertension associated with congenital heart disease.Int J Cardiol. 2013; 164: 64-69
- Long term effects of bosentan treatment in adult patients with pulmonary arterial hypertension related to congenital heart disease (Eisenmenger physiology): safety, tolerability, clinical, and haemodynamic effect.Heart. 2007; 93: 621-625
- Long-term oral bosentan treatment in patients with pulmonary arterial hypertension related to congenital heart disease: a 2-year study.Heart. 2007; 93: 350-354
- Effect of bosentan on exercise capacity and quality of life in adults with pulmonary arterial hypertension associated with congenital heart disease with and without Down's syndrome.Am J Cardiol. 2009; 103: 1309-1315
- Macitentan and morbidity and mortality in pulmonary arterial hypertension.N Engl J Med. 2013; 369: 809-818
- Evaluation of macitentan in patients with Eisenmenger syndrome.Circulation. 2019; 139: 51-63
- Tale of 2 endothelin receptor antagonists in Eisenmenger syndrome.Circulation. 2019; 139: 64-66
- From bosentan to macitentan for pulmonary arterial hypertension and adult congenital heart disease: further improvement?.Int J Cardiol. 2017; 227: 51-52
- Quality of life and functional capacity can be improved in patients with Eisenmenger syndrome with oral sildenafil therapy.Int J Cardiol. 2011; 149: 372-376
- Effects of chronic sildenafil in patients with Eisenmenger syndrome versus idiopathic pulmonary arterial hypertension.Int J Cardiol. 2007; 120: 301-305
- Oral sildenafil treatment for Eisenmenger syndrome: a prospective, open-label, multicentre study.Heart. 2011; 97: 1876-1881
- A randomized, placebo-controlled, double-blind, crossover study to evaluate the efficacy of oral sildenafil therapy in severe pulmonary artery hypertension.Am Heart J. 2006; 151 (851.e851-5)
- Clinical efficacy of phosphodiesterase-5 inhibitor tadalafil in Eisenmenger syndrome: a randomized, placebo-controlled, double-blind crossover study.Congenit Heart Dis. 2011; 6: 424-431
- Phosphodiesterase-5 inhibitor in Eisenmenger syndrome: a preliminary observational study.Circulation. 2006; 114: 1807-1810
- Usefulness of epoprostenol therapy in the severely ill adolescent/adult with Eisenmenger physiology.Am J Cardiol. 2003; 91: 632-635
- Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects.Circulation. 1999; 99: 1858-1865
- Long-term effects of continuous prostacyclin therapy in adults with pulmonary hypertension associated with congenital heart disease.Int J Cardiol. 2013; 168: 4117-4121
- Effects of inhaled iloprost on exercise capacity, quality of life, and cardiac function in patients with pulmonary arterial hypertension secondary to congenital heart disease (the Eisenmenger syndrome) (from the EIGER Study).Am J Cardiol. 2013; 112: 1834-1839
- 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. 2002; 39: 1496-1502
- Selexipag treatment for pulmonary arterial hypertension associated with congenital heart disease after defect correction: insights from the randomised controlled GRIPHON study.Eur J Heart Fail. 2019; 21: 352-359
- Combination therapy with bosentan and sildenafil in Eisenmenger syndrome: a randomized, placebo-controlled, double-blinded trial.Eur Heart J. 2010; 31: 1124-1131
- Bosentan-sildenafil association in patients with congenital heart disease-related pulmonary arterial hypertension and Eisenmenger physiology.Int J Cardiol. 2012; 155: 378-382
- Risks and benefits of exercise training in adults with congenital heart disease.Can J Cardiol. 2016; 32: 459-466
- Heart-lung transplantation for Eisenmenger syndrome: early and long-term results.Ann Thorac Surg. 2001; 72: 1887-1891
- Bilateral lung transplantation with closure of ventricular septal defect in a patient with Eisenmenger syndrome.Gen Thorac Cardiovasc Surg. 2010; 58 (discussion 29): 25-28
- Heart-lung transplantation for end-stage heart disease with Eisenmenger's syndrome: report of two cases.Chin Med J (Engl). 2009; 122: 2189-2192
- Misperception of survival in adult congenital heart disease and importance of of both anatomoic and functional indices: educate your patients!.Can J Cardiol. 2019; 35: 1635-1639
Article info
Publication history
Published online: October 10, 2019
Accepted:
October 1,
2019
Received:
September 30,
2019
Footnotes
See page 1672 for disclosure information.
Identification
Copyright
© 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
