DAILY PRACTICE REVISED

A proposed algorithm for management of patients with congenital cardiac defects associated with pulmonary hypertension

One of the objectives of the Pulmonary Hypertension Associated with Congenital Heart Disease (PAH-CHD) Task Force is to bring up controversial issues to discussion. Two frequent problems in the management of children with PAH-CHD are: 1) to define the need for cardiac catheterization; 2) to decide which patients should undergo complete repair of the anomaly. In developed countries, most children with congenital cardiac shunts are assigned to operation on the basis of noninvasive evaluation only. This is based on the assumption that patients can be considered as at low risk for immediate postoperative complications and late residual pulmonary hypertension if surgical treatment is offered early in life. Although this can be accepted as a general rule, early access to treatment may not be the reality in many underserved areas. Furthermore, young babies with certain anomalies (eg, truncus arteriosus, transposition of the great arteries and complete atrioventricular septal defect) may develop severe pulmonary hypertension early during the first months of life. Some patients with simple anomalies such as nonrestrictive ventricular septal defect or patent ductus arteriosus do not have congestive heart failure or failure to thrive in their clinical history, thus indicating increased pulmonary vascular resistance and absence of increased pulmonary blood flow. Although there is general agreement that direct measurement of pulmonary vascular resistance is necessary in some cases, there hasnt been evidence to support recommendations in terms of catheterization in children with congenital cardiac shunts and elevated pulmonary arterial pressure. There hasnt been evidence to recommend closure of the septal defects with acceptable risk either. In the Task Force, we attempted to develop a simple algorithm for patient management (see at the end of the text). However, before using the algorithm in clinical practice, some considerations are necessary: 1. There is no simple rule to assign children with PAH-CHD to catheterization or operation. Decision must be individualized. 2. Decision should be based on multiple data obtained from the clinical history, physical examination, oxymetry, qualitative and quantitative echocardiographic evaluation and cardiac catheterization if necessary. 3. The criteria that appear in the algorithm are considerably strict. They were adopted as an attempt to ensure a lower risk of postoperative (immediate and late) complications. 4. The algorithm is not applicable to complex situations as is the case of absent subpulmonary ventricle. In this specific situation, even mild postoperative elevation of pulmonary vascular resistance may result in failure of the circuit (cavopulmonary in this case).
-1-

5. Criteria for patient assignment to temporary palliation (pulmonary arterial banding) are not suggested in the algorithm. An interesting point for discussion is the potential impact of the new drugs for pulmonary arterial hypertension on the diagnosis-and- treatment algorithm of PAH-CHD. It is unlikely the availability of these drugs will influence the decision to catheterize, in particular since noninvasive predictors of outcomes have not been developed or validated for this patient population. However, the new therapies may influence the decision to operate in two ways: 1) treatments may decrease the likelihood of residual (persistent) pulmonary hypertension following repair of the defects in OPERABLE patients; 2) one could THEORETICALLY make inoperable patients become operable. While these hypotheses remain to be tested by means of randomized controlled studies, the possibility of combining medical and surgical therapeutic strategies is suggested in the algorithm.

Antonio Augusto Lopes, MD, FPVRI

Dept. Pediatric Cardiology and Adult Congenital Heart Disease The Heart Institute (InCor), University of So Paulo Medical School, So Paulo, Brazil Vice-president for Education, Pulmonary Vascular Research Institute (PVRI) Co-leader, Pulmonary Hypertension Associated with Congenital Heart Disease Taskforce, PVRI

Over the past decade, our ability to successfully perform corrective surgical repair in patients with congenital heart defects and increased pulmonary vascular resistance has improved with advances in anesthesiology, ICU support, development of therapeutic interventions and treatment modalities, (e.g. inhaled nitric oxide, prostacyclin analogues and phosphodiesterase type 5 inhibitors), and utilization of cardiac and pulmonary assist devices, ECMO, atrial septostomy and/or palliative Potts' shunt a(s needed for acute pulmonary hypertension crises peri-operatively). However, just because we "can" carryout these surgical repairs and discharge these patients from the hospital, it remains unclear if long term we are doing what is in the best interests of the patients. We must remain cognizant of the natural history of Eisenmenger Syndrome versus Idiopathic Pulmonary Arterial Hypertension. We must also consider the adverse effects associated with the treatment options short and long term and their cost effects. Our ability to carry patients through a "stormy" peri-operative period has significantly improved but long-term outcomes remain unknown. It is vital if we are to move forward to improve overall quality of life and long term outcomes for children and adults with congenital heart defects who have increased pulmonary vascular resistance, we need to evaluate the patients carefully and follow all the patients long term (i.e. at least 10-20 years and preferably longer) whether they are repaired or not in order for us to determine if what "we are able to do"

-2-

is "what we should be doing." "Benign Neglect", "Do no Harm" and "Better is the Enemy of Good" may be preferable for some patients. Factors other than resting pulmonary vascular resistance are important to consider when assessing a patient for operability. Additional factors include: 1. Age of the patient 2. Pulmonary to systemic blood flow, i.e. Qp/Qs 3. Ratio of pulmonary to systemic vascular resistance, i.e. PVRI/SVRI 4 Associated anomalies, e.g. Down Syndrome, upper airway obstruction 5. Clinical characteristics, e.g. comorbid conditions, concomitant medications, altitude 6. Complexity of the congenital heart defect(s), i.e. simple versus complex congenital heart defects

Robyn J. Barst, MD, FPVRI

Professor Emerita of Pediatrics Columbia University College of Physicians & Surgeons New York, New York, USA Fellow, Pulmonary Hypertension Associated with Congenital Heart Disease Taskforce, Pulmonary Vascular Research Institute (PVRI) Co-Leader, Sponsored International Fellowships Taskforce, PVRI

Management of patients with congenital cardiac septal defects associated with pulmonary hypertension
L R shunting CHF (pulmonary congestion) Failure to thrive SAT O2 >95% - no gradient RUE vs. LEs (acyanotic defects)

PAH-CHD Task Force

PRESENT OPERABLE Postop. PH crises and residual PH may occur in rare instances
Consider: Age Type and size of the defect Associated syndromes

ABSENT

TGA (with or without VSD) Truncus arteriosus Complete AV septal defect Non-restrictive VSD, PDA, Nonaortopulmonary window CATHETERIZATION

Baseline PVRI < 6 unitsm2 units PVRI/SVRI < 0.3

6 Baseline PVRI < 8-9 0.3 PVRI/SVRI < 0.5

Baseline PVRI 8-9 PVRI/SVRI 0.5

AVT* as complementary information

AVT* absolutely necessary

+
CONSIDER OPERATION
*AVT: Acute pulmonary vasodilator test. A positive response is defined as a 20% decrease in PVRI AND PVRI/SVRI ratio, with respective final (lowest) values of < 6 unitsm2 and < 0.3. Preferably use PVRI/SVRI ratio if measured oxygen consumption is not available.

VASODILATOR THERAPY

INOPERABLE

CATH

High risk of serious postop. complications

-3-

References: 1. Adatia I, Beghetti M. Immediate postoperative care. Cardiol Young 2009; 19(E-Suppl. 1): 2327. 2. Atz AM, Adatia I, Lock JE, Wessel DL. Combined effects of nitric oxide and oxygen during acute pulmonary vasodilator testing. J Am Coll Cardiol 1999; 33:813-9. 3. Balzer DT, Kort HW, Day RW, et al. Nitric Oxide as a Preoperative Test (INOP Test I): the INOP Test Study Group. Circulation 2002; 106:I76-81. 4. Barst R, Stewart D. Conventional and targeted medical therapies. Cardiol Young 2009; 19(E-Suppl. 1): 2834. 5. Barst RJ, Maislin G, Fishman AP. Vasodilator therapy for pulmonary hypertension in children. Circulation. 1999; 99:1197-208. 6. Berger RMF. Possibilities and impossibilities in the evaluation of pulmonary vascular disease in congenital heart defects. Eur Heart J 2000; 21:17-27. 7. Berner M, Beghetti M, Spahr-Schopfer I, Oberhansli I, Friedli B. Inhaled nitric oxide to test the vasodilator capacity of the pulmonary vascular bed in children with long-standing pulmonary hypertension and congenital heart disease. Am J Cardiol 1996; 77:532-5. 8. Bush A, Busst CM, Haworth SG, et al. Correlations of lung morphology, pulmonary vascular resistance, and outcome in children with congenital heart disease. Br Heart J 1988; 59:480-5. 9. Giglia TM, Humpl T. Preoperative pulmonary hemodynamics and assessment of operability: is there a pulmonary vascular resistance that precludes cardiac operation? Pediatr Crit Care Med 2010; 11:S57S69. 10. Lopes AA, OLeary PW. Measurement, interpretation and use of hemodynamic parameters. Cardiol Young 2009; 19(E-Suppl. 1): 812. 11. Neutze JM, Ishikawa T, Clarkson PM, et al. Assessment and follow-up of patients with ventricular septal defect and elevated pulmonary vascular resistance. Am J Cardiol 1989; 63:327-31. 12. Rabinovitch M, Keane JF, Norwood WI, Castaneda AR, Reid L. Vascular structure in lung tissue obtained at biopsy correlated with pulmonary hemodynamic findings after repair of congenital heart defects. Circulation 1984; 69:655-67. 13. Rosenzweig EB, Ivy DD, Widlitz A, et al. Effects of long-term bosentan in children with pulmonary arterial hypertension. J Am Coll Cardiol. 2005; 46:697-704. Comment in: J Am Coll Cardiol. 2005; 46:705-706. J Am Coll Cardiol. 2006; 47:1914-1915; author reply 1915. 14. Rosenzweig EB, Kerstein D, Barst RJ. Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects. Circulation 1999; 99:1858-65. 15. Turanlahti MI, Laitinen PO, Pesonen EJ. Preoperative and postoperative response to inhaled nitric oxide. Scand Cardiovasc J 2000; 34:46-52. 16. Wilkinson JL. Congenital heart disease: haemodynamic calculations in the catheter laboratory. Heart 2001; 85:113-20.

-4-

17. Yamaki S, Abe A, Endo M, Tanaka T, Tabayashi K, Takahashi T. Surgical indication for congenital heart disease with extremely thickened media of small pulmonary arteries. Ann Thorac Surg 1998; 66:1560-4. 18. Yasuda T, Tauchi N, Baba R, et al. Inhalation of low-dose nitric oxide to evaluate pulmonary vascular reactivity in children with congenital heart disease. Pediatr Cardiol 1999; 20:278-82.

-5-