|CURRICULUM IN CARDIOLOGY - PANEL DISCUSSION
|Year : 2019 | Volume
| Issue : 1 | Page : 48-52
Eisenmenger's syndrome: Management and workup for heart–lung transplant
Jay Relan1, Sakshi Sachdeva1, Neeraj Awasthy2, Sivasubramanian Ramakrishnan1
1 Department of Cardiology, AIIMS, New Delhi, India
2 Department of Pediatric Cardiology, Max Super Specialty Hospital, New Delhi, India
|Date of Web Publication||2-May-2019|
Dr. Sakshi Sachdeva
Department of Cardiology, AIIMS, New Delhi
Source of Support: None, Conflict of Interest: None
Heart–lung transplant remains the final option for patients with congenital heart disease (CHD) and irreversible pulmonary vascular obstructive disease (PVOD) when the patients are symptomatic despite optimal medical management. This panel discussion, held during cardiovascular disease convergence 2018, takes us through the journey of an 18-year-old patient suffering from a complex cyanotic CHD with irreversible PVOD and severe ventricular dysfunction. Pertinent management issues concerning pharmacotherapy and supportive care are discussed. Finally, workup and listing criteria for heart–lung transplant are discussed. The patient still awaits heart–lung transplant.
Keywords: Congenital heart disease, Eisenmenger's syndrome, heart–lung transplantation
|How to cite this article:|
Relan J, Sachdeva S, Awasthy N, Ramakrishnan S. Eisenmenger's syndrome: Management and workup for heart–lung transplant. J Pract Cardiovasc Sci 2019;5:48-52
|How to cite this URL:|
Relan J, Sachdeva S, Awasthy N, Ramakrishnan S. Eisenmenger's syndrome: Management and workup for heart–lung transplant. J Pract Cardiovasc Sci [serial online] 2019 [cited 2019 Dec 11];5:48-52. Available from: http://www.j-pcs.org/text.asp?2019/5/1/48/257594
| Introduction|| |
Heart–lung transplant is the last option for patients with congenital heart disease (CHD) and irreversible pulmonary vascular obstructive disease when the patients are symptomatic despite optimal medical management. In this review, we discuss the clinical issues, management strategies, and pretransplant workup of one such patient.
| Clinical Vignette|| |
18-year-old Mr. S, was a full term, healthy neonate without any perinatal issues. He became symptomatic with onset of fast breathing, feeding difficulty, failure to thrive, and recurrent respiratory infections in early infancy. At 6 months of age, he was detected to have persistent low oxygen saturation during an admission for lower respiratory tract infection. On evaluation, he was diagnosed with a cyanotic CHD-double outlet right ventricle, mitral atresia, hypoplastic left ventricle, nonrestrictive ventricular septal defect, restrictive interatrial communication, severe pulmonary artery hypertension (PAH), and pulmonary venous hypertension. He underwent percutaneous balloon atrial septostomy (BAS) at 1 year of age, following which he symptomatically improved and started gaining weight. Child remained on irregular follow-up and was brought to our center for the first time at 5 years of age.
He was thoroughly evaluated. Cardiac catheterization revealed systemic pulmonary artery (PA) pressures, aortic saturation of 83%, and calculated pulmonary vascular resistance index (PVRI) of 6.2 WU.m2. Because of the unfavorable systemic saturation, he was deemed unsuitable for PA banding. Due to severe PAH and single functioning systemic right ventricle, gradually ventricular dysfunction set in. He had a progressive downhill course with symptoms of cough, breathlessness, easy fatigability, orthopnea, and edema, needing repeated hospitalizations every 3–4 months. During each admission, he required intravenous diuretics, inotropes (dobutamine and dopamine), vasodilators (nitroglycerine), oxygen, and antibiotics for stabilization.
At the age of 16 years, he underwent BAS again in view of restrictive interatrial communication [Table 1], but the symptoms did not improve significantly. He was continued on multiple medications, which included pulmonary vasodilators (bosentan and sildenafil), angiotensin-converting enzyme (ACE) inhibitor, diuretics and digoxin, along with salt and water restriction. Despite maximal tolerable medical therapy, he remained in the WHO functional class (FC) III with intermittent deterioration to Class IV. Hence, after extensive counseling and discussion with family, he was planned for heart–lung transplant. His pretransplant workup included multiple blood and radiological investigations and functional assessments following which he was listed for heart–lung transplant. His chest radiograph, 12-lead electrocardiogram and echocardiogram are shown in [Figure 1]. He is still awaiting heart–lung transplant.
|Table 1: Cardiac catheterization hemodynamic data at the time of balloon atrial septostomy depicting pressure gradient between the left and the right atrium due to patent foramen ovale restriction|
Click here to view
|Figure 1: (a) Electrocardiogram of the patient depicting right atrial enlargement, right ventricular dominance and hypertrophy with left axis deviation. (b) Chest radiograph, Postero-anterior view showing cardiomegaly with right atrial enlargement, right ventricular type apex, malposed great vessels, and pruning of peripheral vascularity in lung fields. Skeletal deformity in form of scoliosis is also seen. (c) Echocardiographic image in apical four chamber view showing mitral valve atresia, dilated right atrium and right ventricle.|
Click here to view
| Questions to Panelists|| |
Question: When should PAH-targeted therapy be started in patients with Eisenmenger's syndrome (ES)?
Answer: Initiation of PAH-targeted therapy is strongly recommended in patients with the WHO FC III. Evidence is stronger for the use of endothelin receptor antagonists (ERAs) than phosphodiesterase-5 (PDE-5) inhibitors.,,,,,, There is lack of evidence for the use of PAH-targeted therapy in ES patients in FC II and is hence not routinely recommended. Patients with ES in FC II should be assessed for the presence of adverse prognostic features, including brain natriuretic peptide levels, C-reactive protein levels, and 6-min walk distance which may support initiation of PAH-targeted therapy.,,
Question: Which one of the two, ERA/PDE-5 inhibitors, should we start with? When should the 2nd drug be added? Is there any role of upfront combination therapy?
Answer: The choice of initial therapy is influenced by factors such as side effects, interactions, and contraindications. Routine upfront or early sequential oral combination therapy is not supported by the existing literature in patients with ES, unlike in idiopathic pulmonary hypertension. Combination therapy with an ERA and PDE-5 inhibitors should be considered in patients with markers of adverse outcome or clinical deterioration while on monotherapy.,, Annual influenza and pneumococcal vaccination are also recommended.
Question: What causes hemoptysis in patients with ES?
Answer: The causes of hemoptysis in ES include aortopulmonary collaterals, pulmonary thrombosis, pulmonary tuberculosis, and pulmonary artery (PA) dissection. Approximately 40% of patients develop hemoptysis and treating the cause results in symptom remission in 45% of the cases. Hence, computerized tomographic pulmonary angiography is recommended in an ES patient presenting with hemoptysis.,
Question: What is the role of anticoagulation? What should be the target international normalized ratio (INR)?
Answer: Endothelial dysfunction and an imbalance between procoagulant and anti-thrombotic factors results in thrombotic vasculopathy in ES patients. Almost 20% of ES patients have PA thrombus. Anticoagulation should be started in ES patients with atrial fibrillation, pulmonary or systemic thromboembolism and those in congestive heart failure due to significant ventricular dysfunction. It should be continued in patients who do not have significant hemoptysis or other bleeding risks. Target INR should be around 2.5 depending on the risk factors. It does not provide any survival benefit in those without risk factors for thrombosis.
Question: What is the role of beta-blockers? Which beta-blocker should be preferred?
Answer: Literature regarding the use of beta-blockers in ES is scarce. They help to control the heart rate and improve ventricular filling in the setting of diastolic dysfunction. Beta-blockers have a role in recurrent arrhythmia prevention. They may also help in better ventricular remodeling. However, their use in the acutely symptomatic phase results in significant hemodynamic worsening in patients with ES. The preferred beta-blocker for use may be carvedilol.,
Question: Are ACE inhibitors useful or harmful?
Answer: In earlier days, ACE inhibitors used to be avoided, anticipating the risk of fall in systemic vascular resistance (SVR) and thus an increase in physiological right to left shunt, resulting in worsening of cyanosis in ES patients. Literature supporting their use is scanty. In a small study, ACE inhibitors were found to improve systemic output, mixed venous saturation, cyanosis, and FC in adult patients with cyanotic CHD.
Question: Is there a role of digoxin in managing such patients?
Answer: Digoxin has been used in ES patients for a long time without sufficient evidence. It may worsen the symptoms of the patient. The current role for digoxin is limited to patients with congestive heart failure and in the presence of atrial fibrillation.
Question: Any role of home oxygen therapy?
Answer: Existing literature does not support the routine prescription of home oxygen therapy. Its use should be individualized and continued only if there is clear benefit to the patient.,
Question: What is the best method for assessing iron deficiency in these patients?
Answer: Approximately one-third of ES patients suffer from iron deficiency which is due to reduced absorption and increased consumption of iron from erythrocytosis and chronic bleeding. Transferrin saturation and serum ferritin are the most commonly used parameters to assess iron status.,
Question: When should we consider venesection/partial exchange transfusion in these patients?
Answer: Routine venesection in ES patients is contraindicated due to an increased risk of cerebrovascular events. The only indication for venesection is the presence of neurological symptoms of hyperviscosity in iron-replete patients with high hematocrit (>0.65) after ruling out dehydration and cerebral abscess.,
Question: What are the risks of noncardiac surgery in these patients? How to manage these patients in the perioperative period?
Answer: Perioperative risks of cardiac surgery in ES patients include increased cyanosis due to decrease in SVR, increased risk of developing arrhythmias, bleeding, and thromboembolic complications. There is a mortality risk of 3.5%–18%, with the risk being higher in emergency and prolonged surgeries. The predictors of outcome include the degree of exercise intolerance, severity of pulmonary hypertension, and requirement for inotropic support. Risk reduction strategies include minimizing blood loss, avoidance of sudden reduction in SVR or rise in PVR, and minimizing the negative cardiovascular effects of positive airway pressure support. PAH-targeted therapies should be continued. The use of vasopressor agents to maintain SVR and intravenous prostanoids to reduce PVR may be considered in the perioperative period., Air embolism should be avoided using air filters.
Question: What are the criteria for listing for heart–lung transplant?
Answer: Patient should be in INTERMACS Class III or less to be listed for transplant.
Absolute contraindications should be ruled out, which include uncontrolled or untreatable pulmonary or extra pulmonary infection; active Mycobacterium tuberculosis infection; malignancy in the past 2 years; significant dysfunction of other vital organs; uncorrectable bleeding diathesis; significant chest wall/spinal deformity; Class II or III obesity: body mass index (BMI) ≥35 kg/m2; active tobacco smoking; drug or alcohol dependency; and unresolved psychosocial problems or noncompliance with medical therapy.
Relative contraindications to heart–lung transplant include age > 65 years; Class I obesity: BMI 30–34.9 kg/m2; severe or progressive malnutrition; severe symptomatic osteoporosis; extensive prior thoracic surgery with lung resection; infection with highly resistant or highly virulent bacteria, fungi, and certain strains of mycobacteria; HIV infection; ongoing hepatitis B or C viral infection; absence of a consistent or reliable social support system.
Question: What all investigations are done as part of pretransplant work-up?
Answer: Pretransplant workup includes multiple blood and radiological investigations, and functional assessments. Anthropometric measurements are taken and vaccination is completed. [Table 2] lists the recommended pretransplant workup.
Question: Is heart–lung transplantation a better strategy than lung transplantation with repair of cardiac defect?
Answer: There is limited literature comprising small numbers comparing the two strategies. Waddell et al. analyzed the United Network for Organ Sharing/International Society for Heart–Lung Transplantation joint transplant registry comparing the two strategies in 605 patients with ES. Combined heart and lung transplantation appeared to be the safer procedure, with a significantly higher survival rate in comparison to lung transplantation with intracardiac repair (P = 0.002). The procedure of choice for ES patients with ventricular septal defect, complex anatomy, or significant left or right ventricular dysfunction remains heart–lung transplantation. The polarity of opinion persists in this area because of the genuine issue of donor organ availability. ES patients with simple cardiac anomalies such as atrial septal defect and patent ductus arteriosus can be treated with a combination of lung transplantation and cardiac repair unless precluded by severe ventricular dysfunction.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
The authors would like to thank Prof. S.S. Kothari for constructive suggestions.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Galiè N, Beghetti M, Gatzoulis MA, Granton J, Berger RM, Lauer A, et al.
Bosentan therapy in patients with Eisenmenger syndrome: A multicenter, double-blind, randomized, placebo-controlled study. Circulation 2006;114:48-54.
Gatzoulis MA, Beghetti M, Galiè N, Granton J, Berger RM, Lauer A, et al.
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.
Stout KK, Daniels CJ, Aboulhosn JA, Bozkurt B, Broberg CS, Colman JM, et al
. 2018 AHA/ACC guideline for the management of adults with congenital heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;139:e698-e800.
Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, 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 2016;37:67-119.
Gatzoulis MA, Landzberg M, Beghetti M, Berger RM, Efficace M, Gesang S, et al.
Evaluation of macitentan in patients with Eisenmenger syndrome. Circulation 2019;139:51-63.
Mukhopadhyay S, Nathani S, Yusuf J, Shrimal D, Tyagi S. Clinical efficacy of phosphodiesterase-5 inhibitor tadalafil in Eisenmenger syndrome – A randomized, placebo-controlled, double-blind crossover study. Congenit Heart Dis 2011;6:424-31.
Singh TP, Rohit M, Grover A, Malhotra S, Vijayvergiya R. 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.e1-5.
Diller GP, Alonso-Gonzalez R, Kempny A, Dimopoulos K, Inuzuka R, Giannakoulas G, et al.
B-type natriuretic peptide concentrations in contemporary Eisenmenger syndrome patients: Predictive value and response to disease targeting therapy. Heart 2012;98:736-42.
Martin-Garcia AC, Arachchillage DR, Kempny A, Alonso-Gonzalez R, Martin-Garcia A, Uebing A, et al.
Platelet count and mean platelet volume predict outcome in adults with Eisenmenger syndrome. Heart 2018;104:45-50.
Kempny A, Dimopoulos K, Alonso-Gonzalez R, Alvarez-Barredo M, Tutarel O, Uebing A, et al.
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;168:4784-9.
Iversen K, Jensen AS, Jensen TV, Vejlstrup NG, Søndergaard L. Combination therapy with bosentan and sildenafil in Eisenmenger syndrome: A randomized, placebo-controlled, double-blinded trial. Eur Heart J 2010;31:1124-31.
D'Alto M, Romeo E, Argiento P, Sarubbi B, Santoro G, Grimaldi N, et al.
Bosentan-sildenafil association in patients with congenital heart disease-related pulmonary arterial hypertension and Eisenmenger physiology. Int J Cardiol 2012;155:378-82.
Condliffe R, Clift P, Dimopoulos K, Tulloh RM. Management dilemmas in pulmonary arterial hypertension associated with congenital heart disease. Pulm Circ 2018;8:2045894018792501.
Ramakrishnan S, Gupta SK, Jo J, Gulati G, Juneja R, Kothari SS, et al
. Causes of hemoptysis in Eisenmenger syndrome – A CT angiography study. Indian Heart J 2014;66:S55.
Cantu J, Wang D, Safdar Z. Clinical implications of haemoptysis in patients with pulmonary arterial hypertension. Int J Clin Pract Suppl 2012;66:5-12.
Broberg CS, Ujita M, Prasad S, Li W, Rubens M, Bax BE, et al.
Pulmonary arterial thrombosis in Eisenmenger syndrome is associated with biventricular dysfunction and decreased pulmonary flow velocity. J Am Coll Cardiol 2007;50:634-42.
Roldan T, Landzberg MJ, Deicicchi DJ, Atay JK, Waxman AB. Anticoagulation in patients with pulmonary arterial hypertension: An update on current knowledge. J Heart Lung Transplant 2016;35:151-64.
Sandoval J, Santos LE, Córdova J, Pulido T, Gutiérrez G, Bautista E, et al.
Does anticoagulation in Eisenmenger syndrome impact long-term survival? Congenit Heart Dis 2012;7:268-76.
Grinnan D, Bogaard HJ, Grizzard J, Van Tassell B, Abbate A, DeWilde C, et al.
Treatment of group I pulmonary arterial hypertension with carvedilol is safe. Am J Respir Crit Care Med 2014;189:1562-4.
Ramakrishnan S, Vyas C, Kothari SS, Bhargava B, Kukreti BB, Kalaivani M, et al.
Acute and short-term hemodynamic effects of metoprolol in Eisenmenger syndrome: A preliminary observational study. Am Heart J 2011;161:938-43.
Hopkins WE, Kelly DP. Angiotensin-converting enzyme inhibitors in adults with cyanotic congenital heart disease. Am J Cardiol 1996;77:439-40.
Diller GP, Körten MA, Bauer UM, Miera O, Tutarel O, Kaemmerer H, et al.
Current therapy and outcome of Eisenmenger syndrome: Data of the German national register for congenital heart defects. Eur Heart J 2016;37:1449-55.
Gonzaga LR, Matos-Garcia BC, Rocco IS, Begot I, Bolzan DW, Tatani SB, et al.
Effects of acute oxygen supplementation on functional capacity and heart rate recovery in Eisenmenger syndrome. Int J Cardiol 2017;231:110-4.
Sandoval J, Aguirre JS, Pulido T, Martinez-Guerra ML, Santos E, Alvarado P, et al.
Nocturnal oxygen therapy in patients with the Eisenmenger syndrome. Am J Respir Crit Care Med 2001;164:1682-7.
Kaemmerer H, Fratz S, Braun SL, Koelling K, Eicken A, Brodherr-Heberlein S, et al.
Erythrocyte indexes, iron metabolism, and hyperhomocysteinemia in adults with cyanotic congenital cardiac disease. Am J Cardiol 2004;94:825-8.
Ammash N, Warnes CA. Cerebrovascular events in adult patients with cyanotic congenital heart disease. J Am Coll Cardiol 1996;28:768-72.
Ramakrishna G, Sprung J, Ravi BS, Chandrasekaran K, McGoon MD. Impact of pulmonary hypertension on the outcomes of noncardiac surgery: Predictors of perioperative morbidity and mortality. J Am Coll Cardiol 2005;45:1691-9.
Price LC, Dimopoulos K, Marino P, Alonso-Gonzalez R, McCabe C, Kemnpy A, et al.
The CRASH report: Emergency management dilemmas facing acute physicians in patients with pulmonary arterial hypertension. Thorax 2017;72:1035-45.
Stevenson LW, Pagani FD, Young JB, Jessup M, Miller L, Kormos RL, et al.
INTERMACS profiles of advanced heart failure: The current picture. J Heart Lung Transplant 2009;28:535-41.
Waddell TK, Bennett L, Kennedy R, Todd TR, Keshavjee SH. Heart-lung or lung transplantation for Eisenmenger syndrome. J Heart Lung Transplant 2002;21:731-7.
Olland A, Falcoz PE, Canuet M, Massard G. Should we perform bilateral-lung or heart – lung transplantation for patients with pulmonary hypertension? Interact Cardiovasc Thorac Surg 2013;17:166-70.
[Table 1], [Table 2]