RECOMMENDATIONS FOR THE MANAGEMENT OF ADULTS WITH CONGENITAL HEART DISEASE - 2001 (PART 3)
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Table of Contents
Section XI - Complete Transposition of the Great Arteries
Part l - Background Information
Definition: There is atrioventricular concordance and ventriculoarterial discordance - i.e. the right atrium connects to the morphological right ventricle which gives rise to the aorta and the left atrium connects to the morphological left ventricle which gives rise to the pulmonary artery.
Approximately 2/3 of patients have no major associated abnormalities ("simple" transposition). Approximately 1/3 have associated abnormalities ("complex" transposition). The most common associated abnormalities are VSD and pulmonary/subpulmonary stenosis.
Unoperated (simple) transposition is a lethal condition with 90% mortality in the first year of life. Thus nearly all patients seen as adults will have had intervention.
The most common surgical procedure in patients who are currently adults is the atrial switch operation in the form of a Mustard or a Senning procedure. Blood is redirected at the atrial level using a baffle (Mustard operation) or atrial flaps (Senning operation), achieving physiological correction, but the right ventricle continues to support the systemic circulation.
Now, the atrial switch operation has been supplanted by the arterial switch operation (Jatene), but few of these patients have yet become adults. Blood is redirected at the great artery level by switching the aorta and pulmonary arteries such that the left ventricle supports the systemic circulation. The coronary arteries are translocated to the neo-aorta (formerly the pulmonary artery). The tissue loss in the sinuses of the neo-pulmonary artery is made good with a pericardial patch.
In a small proportion of patients (<10%) who have VSD and pulmonary/subpulmonary stenosis, a Rastelli operation will have been done. Blood is redirected at the ventricular level (with the left ventricular outflow tunnelled to the aorta) and a valved conduit is placed from the right ventricle to the aorta. The left ventricle supports the systemic circulation.
Rarely, in patients with a large VSD and established pulmonary vascular disease, a palliative atrial switch operation will have been done to improve oxygenation. This is an atrial switch operation but the VSD is left open (or enlarged). These patients resemble Eisenmenger VSDs and should be managed as such. (See Eisenmenger Section XV).
Since most patients will have had an operation, investigations are directed towards post-operative sequelae and will vary according to the type of operation performed.
All patients should have at a minimum:
The following are possible intervention strategies:
The overall survival of patients who have had an atrial switch procedure is approximately 65% at 25 years, with increased likelihood of survival with later year of operation. Patients who have "simple" transposition have a better survival (80% at 25 years) than those with "complex" transposition (45% at 25 years). Causes of death include sudden unexpected (presumed arrhythmic) death, heart failure and baffle obstruction.
The long-term survival data following the arterial switch is just beginning to emerge (169). Neo-aortic root dilation, neo-aortic valve regurgitation, right ventricular outflow tract obstruction and coronary artery stenosis/occlusion are recognized complications.
Following the Rastelli operation repeated conduit changes will be necessary and there is a risk of deteriorating ventricular function. Sustained monomorphic ventricular tachycardia and supraventricular tachycardias may occur.
Patients who have had a palliative atrial switch probably have a prognosis similar to Eisenmenger VSD but specific information is lacking. Quality of life is generally improved for a time, however.
Atrial flutter (intra-atrial re-entry) occurs in 20% of atrial switch patients by age 20 and progressive sinus node dysfunction and/or junctional rhythm is seen in half of the patients by that time (156,160,161, 173,174).
Transvenous pacemaker insertion for symptomatic bradycardia or anti-tachycardia pacing for some atrial arrhythmias may be required. In patients with an atrial switch operation, transvenous pacing leads must traverse the upper limb of the atrial switch to enter the morphological left atrium and/or left ventricle. Active fixation is required.
Trans-catheter ablation procedures for intra-atrial re-entry tachycardia/atrial flutter and AV nodal re-entry is feasible, with an initial rate of success in these pts of 60-70% (175). Ablation in these patients is more complex and associated with a lower cure rate both because of the complex anatomy and the previous surgical scars; ablation should be undertaken by an electrophysiologist with appropriate training/experience in this population.
Pregnancy in women with a normal functional class following atrial switch operation is usually well tolerated. Worsening of systemic right ventricular function during or shortly after pregnancy, however, is reported in about 10% of patients (176,177). ACE inhibitors should be stopped before pregnancy occurs.
Section XII - Congenitally Corrected Transposition of the Great Arteries
Part I - Background Information
This condition involves atrioventricular discordance and ventriculoarterial discordance (double discordance). Systemic venous return to the right atrium enters the morphological left ventricle, which ejects blood into the pulmonary artery. Pulmonary venous return is to the left atrium and then via the morphological right ventricle to the aorta. The circulation is physiologically corrected but the systemic circulation is supported by the morphologic right ventricle (hence the term 'ventricular inversion' that has been used for this condition).
Congenitally corrected transposition may exist in the setting of univentricular heart, but this is not considered further here.
It is rare (< 1% of CHD) but accounts for a high percentage of cyanotic patients undergoing surgery as adults. Associated anomalies occur in up to 98% in some series and consist of VSD (75% of cases), pulmonary or subpulmonary stenosis (75% of cases) and systemic (tricuspid) valve anomalies (Ebstein-like in 30% of cases). Congenital complete heart block occurs in 5%.
A large survey did not show an elevated rate of cardiac malformations in parents (0.6%) or siblings (0.8%) of patients with different forms of TGA (178). Although single case reports of chromosome 22q11 deletion in cases of TGA exist, a large study did not confirm this association (179).
Patients with no associated abnormalities may survive until the 6th or 7th decade and may go unrecognized until problems arise. Progressive systemic (tricuspid) AV valve regurgitation and systemic (right) ventricular dysfunction which may present as acute pulmonary edema tend to occur from the 4th decade onwards. The presence of significant systemic tricuspid AV regurgitation impacts negatively on the survival of this patient population (180). Atrial arrhythmias are common from the 5th decade onwards. In addition to congenital complete atrioventricular block, acquired complete atrioventricular block continues to develop at 2% per year (181), and is especially common at the time of heart surgery. Pulmonary (mitral) AV valve regurgitation may occasionally occur and subpulmonary (morphological left) ventricular dysfunction or outflow tract obstruction may also develop and progress.
The outcome of patients with pulmonary stenosis/VSD who have a balanced pulmonary circulation (without excessive pulmonary blood flow on the one hand or excessive pulmonary stenosis on the other hand) is similar with or without operation.
An adequate diagnostic workup:
Patients with a VSD and pulmonary outflow tract obstruction are frequently cyanotic and may have been palliated with systemic-to-pulmonary artery shunts in childhood. Significant cyanosis (< 90%) in the absence of severe pulmonary hypertension should be an indication for intracardiac repair.
Occasional patients may be unsuitable for repair because of small pulmonary arteries, small systemic (right) ventricles or straddling AV valves and may require palliative shunt procedures.
VSD closure alone is almost always done in childhood with the VSD patch placed to avoid atrioventricular block.
Balloon dilation of pulmonary stenosis may lead to complete AV block and is not recommended.
Repair may involve implantation of a valved conduit from the pulmonary (left) ventricle to the pulmonary artery and repair of the VSD(s). Alternatively, the Ilbawi approach involves tunnelling the left ventricle to the aorta, a right ventricle-to-pulmonary artery conduit and an atrial switch (Mustard) with/without a bi-directional cavo-pulmonary anastomosis. Thus the morphological left ventricle and mitral valve support the systemic circulation. Adult data is lacking regarding the use of the Ilbawi approach (in the setting of VSD and pulmonary stenosis) or a double switch (i.e. Mustard operation and an arterial switch if there is no pulmonary stenosis). Such procedures should still be considered experimental in adult patients.
Patients with deteriorating systemic (right) ventricular function (which commonly appears after surgical repair) should be treated aggressively with medical therapy but may need to be considered for transplantation. Deterioration may be rapid. The role of ACE inhibitors and beta-blockers in preserving systemic right ventricular function is as yet unknown but many patients are treated empirically with afterload reduction while clinical trial data is awaited.
Complete AV block is not uncommon after surgery and necessitates pacing.
In isolated pulmonary/subpulmonary stenosis, direct enlargement of the outflow tract and valve is seldom possible because of the wedging of the outflow tract and the close relation to the conducting system and left coronary artery, and a pulmonary (left) ventricle-to-pulmonary artery conduit is required.
Of patients with congenitally corrected transposition operated or unoperated who reach adulthood, median survival is 40 years. Survival is better if there are no associated anomalies but the overall survival of these patients is still very poor compared to the general population (190). Usual causes of death are sudden (presumed arrhythmic) and progressive ventricular dysfunction with systemic (tricuspid) AV valve regurgitation.
Following surgical repair of VSD and/or subpulmonary stenosis, rapidly progressive systemic (tricuspid) AV valve regurgitation is well recognized. Medical therapy is often tried, but valve replacement is usually required.
Atrial fibrillation is common in operated patients and may be related to systemic (tricuspid) AV valve regurgitation.
If atrial fibrillation occurs, both anticoagulants and antiarrhythmic therapy are usually required. Back-up pacing may also be necessary. Reparative surgery at the tricuspid valve level does not seem to prevent recurrence of atrial arrhythmias (191).
Complete atrioventricular block requires the insertion of a permanent pacemaker. The optimal modality is DDD but is not always possible. Active fixation electrodes are required.
Pregnancy may be associated with a marked deterioration in systemic right ventricular function and/or the development or worsening of systemic (tricuspid) AV valve regurgitation. In two series of 19 and 22 patients with CCTGA a total of 105 pregnancies were reported (192,193). There were no maternal deaths, but substantial maternal morbidity and fetal losses were observed. Close supervision of such pregnant patients is recommended.
Section XIII - Fontan Operation
Part I - Background Information
The Fontan operation is a palliative procedure for patients with a functionally or anatomically single ventricle or complex malformation considered unsuitable for biventricular repair. There is diversion of all of the systemic venous return to the pulmonary arteries, usually without employing a subpulmonary ventricle.
Originally described for patients with tricuspid atresia, it has now been extended to most forms of single ventricle circulation.
There are numerous variations in the surgical approach. The most likely types of Fontan procedure to be encountered today are: 1) the direct RA-PA connection; 2) the total cavopulmonary connection (SVC to PA and IVC to PA through an intra-atrial tunnel); 3) the extra cardiac conduit (SVC to PA and IVC to PA through an external conduit); and 4) RA-RV through a valved conduit when RV size and function is adequate. The Fontan procedure may be done as a single or staged procedure (with a classic or bi-directional Glenn shunt performed as the first procedure, followed by the completion of the Fontan as a second procedure).
Patients who have had a Fontan operation are at risk from the following:
Particular attention should be paid to:
All patients should have at a minimum:
The following are possible intervention strategies:
The Fontan operation remains a palliative, not a curative, procedure.
The reported average 10-year survival following Fontan operation is approximately 60% rising to 80% under ideal circumstances (204,205).
If PLE develops, the 5-year survival is approximately 50%. Reoperation following the Fontan procedure carries a high mortality, and with PLE the mortality may be as high as 75%. If obstruction in the Fontan circuit is the cause of the PLE, however, successful revision of the Fontan anastomosis may cure the PLE.
Usual causes of death are those related to ventricular failure, arrhythmias, reoperation and PLE.
Atrial flutter/fibrillation is common (15-20% at 5 year follow up), and increases with duration of follow-up. It carries significant morbidity, can be associated with profound hemodynamic deterioration, and needs prompt medical attention. Patients at greater risk for atrial tachyarrhythmias are those who were operated on at an older age, with an atriopulmonary connection, with poor ventricular function, systemic atrioventricular valve regurgitation or increased pulmonary artery pressure. When atrial flutter/fibrillation are present, an underlying hemodynamic cause should always be sought, and in particular, evidence for obstruction of the Fontan circuit needs to be sought. Patients not anticoagulated, presenting in atrial flutter/fibrillation should have intravenous heparin started immediately and transesophageal echocardiography performed to rule out the presence of thrombus. Prompt attempts should be made to restore sinus rhythm if no thrombus is found and/or if there is hemodynamic compromise. Antiarrhythmic medications, alone or combined with an antitachycardia pacing device, and radiofrequency catheter ablation techniques, have had limited success. Surgical conversion from an atriopulmonary Fontan to a total cavopulmonary connection with concomitant atrial cryoablation (for flutter) therapy and maze procedure (for fibrillation) at the time of surgery has been reported with good short-term success (206). Patients with atrial arrhythmias (including paroxysmal) should be anticoagulated with coumadin long-term.
Sinus node dysfunction and complete heart block can occur and require pacemaker insertion. Endovenous ventricular pacing through the coronary sinus is possible but epicardial A-V sequential pacing should be employed whenever possible to reduce the risk of thromboembolism.
Pregnancy carries additional risks to the mother because of the increased hemodynamic burden on the single ventricle and atrium. There is an increased risk of:
Section XIV - Single Ventricles
Part I - Background Information
Patients with single ventricles either have an "anatomically" single ventricle made up of a single pouch of indeterminate origin or, more commonly, have a "functionally" single ventricle with one well-formed ventricle accompanied by a second underdeveloped or rudimentary ventricle. The atrium can be situs solitus, inversus or ambiguous. The atrioventricular valves guarding the inlet of the univentricular heart can consist of either two separate valves (double inlet left ventricle [DILV], double inlet right ventricle [DIRV]) one patent valve and one atretic valve (tricuspid atresia [TA], mitral atresia [MA]) or of a common type (unbalanced AV septal defect). The well-developed ventricular chamber can be of the left ventricular type with an anterosuperior right ventricular pouch or less commonly, of a right ventricular type with a posterior left ventricular pouch (DIRV). The ventriculo-arterial connection can be concordant or discordant, or the great arteries can arise from the same ventricle and be patent or stenotic (209,210).
Patients with an "ideal" anatomy (i.e. a functionally single morphological left ventricle) with a "well balanced" circulation (i.e. some degree of pulmonic stenosis to avoid excessive pulmonary blood flow) may achieve late survival with good ventricular function, exercise capacity and minimal symptoms (211). The prognosis of all patients with unoperated univentricular hearts, however, is poor with a median survival of 14 years (death rate of 4.8% per year) with the majority being symptomatic with cyanosis and exercise intolerance (212).
An initial diagnostic workup should:
Significant functional limitation, resting saturation < 90%, dilated (volume overloaded) systemic ventricle, and paradoxical embolism.
Aortopulmonary shunt. Rarely done as the sole intervention any more.
Bi-directional Glenn. Usually performed in infancy as a staged procedure before the Fontan procedure (1 ventricle repair) or performed as a "definitive palliation" when patients are too high risk for Fontan surgery. It provides a controlled source of pulmonary blood flow while volume unloading the systemic ventricle (213).
Bi-directional Glenn + additional pulmonary blood flow. An additional source of pulmonary blood flow via the pulmonary artery through a pulmonary artery band or native pulmonary stenosis, or through a Blalock-Taussig shunt is sometimes added in conjunction with a bi-directional Glenn procedure in order to increase oxygen saturation at the expense of an increased volume load on the systemic ventricle (214).
1 ventricle repair. Especially when the rudimentary pulmonary ventricle is < 30% of its normal volume, the Fontan procedure will allow systemic venous return to enter directly into the pulmonary circulation, bypassing the pulmonic ventricle or outlet chamber (see Fontan section XIII).
1½ ventricle repair. Sometimes when the rudimentary pulmonic ventricle is between 30-80% of its normal volume, the IVC blood flow will be permitted to return to the pulmonary circulation via the pulmonic ventricle whereas the SVC blood will return directly to the pulmonary circulation via a bi-directional Glenn procedure (215).
2 ventricles repair. In some instances, when the pulmonic ventricle is > 80% of its normal volume, a biventricular repair or ventricular septation may be feasible. Straddling of the AV valves and transposition of the great arteries may complicate this type of repair.
Transplantation. Heart transplantation for ventricular failure or heart and lung transplantation for ventricular failure with pulmonary hypertension should be considered when the patient is symptomatic and further palliation/repair is not possible.
Aortopulmonary shunt. Of the patients that survived to adulthood, there is at best a 50% survival at 20 years follow up (216,217). Systemic ventricular dilation and failure, as well as the development of arrhythmias (mainly atrial fibrillation/flutter), occur commonly.
Bi-directional Glenn. There is a 50% survival at 20 years follow up (217,218). Progressive cyanosis may be due to a greater contribution of IVC blood flow compared to SVC blood flow with somatic growth (as seen in childhood) or, as is typical in adults, from the development of pulmonary arteriovenous fistulae.
Bi-directional Glenn + additional pulmonary blood flow. No long-term studies are available. By increasing volume loading on the systemic ventricle the additional pulmonary blood flow may confer an actual survival disadvantage in these patients (212).
1 ventricle repair. There is an 81% survival at 10 years for "the perfect" Fontan candidate (204) compared to 60% survival at 10 years for all Fontan patients (205). Complications after a Fontan procedure include atrial arrhythmias, thrombus formation, protein losing enteropathy [especially if the Fontan procedure was performed in adults (219)] as well as systemic ventricular failure and progressive AV valve regurgitation. (see Fontan section XIII)
1½ ventricle repair. No long-term studies are available. The main long-term complication of a bi-directional Glenn procedure, namely progressive formation of pulmonary AV fistulae, has not been documented at 4 years follow up following a 1½ ventricular repair (220).
2 ventricle repair. A complex biventricular repair (needing valved conduit or complex intraventricular tunnel) may not be preferable in the short or intermediate term to a simple 1 or 1½ ventricular repair (221).
Transplantation. The outcome of heart transplantation in adult patients with congenital heart disease approaches that of adult patients without congenital heart problems with a 1-year survival of 79% and a 5 year survival of 60% (222). Outcome of heart and lung transplant is less with a 1 year survival of 60-80% and a 10 year survival of 30% (223,224).
Shunt. Patients palliated with an aortopulmonary shunt will develop significantly more atrial fibrillation or flutter at 30 years follow up than patients palliated with a cavopulmonary shunt (35% vs. 15%). Progressive systemic ventricular dysfunction has been linked to the development of atrial arrhythmias (217).
1 ventricle repair. See Fontan section XIII.
Shunt. Pregnancy is often well tolerated in a single ventricle patient with good functional class, good ventricular function and an oxygen saturation > 85%. (See Management of Cyanotic Patients Section XVI). The risk of paradoxical emboli in these patients is high and meticulous attention should be paid to avoid deep venous thrombosis in these patients.
1 ventricle repair. See Fontan section XIII.
Section XV - Eisenmenger syndrome
Part I - Background Information
Eisenmenger syndrome, a term first used by Paul Wood, is defined as pulmonary vascular obstructive disease that develops as a consequence of a large pre-existing left-to-right shunt such that pulmonary artery pressures approach systemic levels and the direction of the flow becomes bi-directional or right-to-left (225). Congenital heart defects that can lead to the Eisenmenger syndrome include "simple" defects such as ASD, VSD and PDA as well as more "complex" defects such as AVSD, truncus arteriosus, aortopulmonary window, complex pulmonary atresia and univentricular heart. The high pulmonary vascular resistance is usually established in infancy (by age 2 years, except in ASD) and can sometimes be present from birth.
Part II - History and Management of Unoperated Patients
Patients with defects that allow free communication between the pulmonary and systemic circuits at the aortic or ventricular levels usually have a fairly healthy childhood (if no early congestive heart failure), and gradually become progressively cyanotic with each succeeding decade. Exercise intolerance (dyspnea and fatigue) is proportional to the degree of hypoxemia or cyanosis. In the absence of complications, these patients generally have a good functional capacity up to their third decade (226,227) and thereafter usually experience a slowly progressive decline in their physical abilities.
In patients with medium or large ASDs, Eisenmenger physiology usually appears later, often associated with pregnancy, recurrent thromboembolism, or the development of primary or other secondary cause of pulmonary hypertension. Such additional factors may be required in ASD patients to develop this physiology, although this is a contentious point.
Complications from Eisenmenger syndrome tend to occur from the third decade onward. Congestive heart failure, the most serious complication, usually occurs after age 40 (226). Other complications include:
Most patients with Eisenmenger survive to adulthood (227-229) with a reported 77% and 42% survival rate at 15 and 25 years of age (227).
The most common modes of death are sudden death (30%), congestive heart failure (25%), and hemoptysis (15%). Pregnancy, perioperative mortality following noncardiac surgery, and infectious causes (brain abscesses and endocarditis) account for most of the remainder (226,227,229).
An adequate diagnostic workup:
The diagnostic workup should include at a minimum:
The diagnostic workup may require:
The current underlying management principle in patients with Eisenmenger syndrome is to avoid any factors that may destabilize the delicately balanced physiology. In general, an approach of non-intervention is recommended.
The main interventions, therefore, are directed toward preventing complications (e.g. flu shots to reduce the morbidity of respiratory infections) or to restore the physiologic balance (e.g. iron replacement for iron deficiency; antiarrhythmic management of atrial arrhythmias; salt restriction and diuretics for right-sided heart failure, etc).
Hyperviscosity symptoms, in the absence of volume depletion, should be treated with isovolumic phlebotomy unless iron deficiency is present in which case iron supplementation (and not phlebotomy) becomes the treatment of choice (see Medical management of cyanotic congenital heart disease Section XVI).
Hypovolemia should be avoided. Any cause of hypovolemia may lead to hypotension and hypoxemia. Volume expansion should be provided immediately.
Noncardiac surgery should be performed only when necessary because of its high associated mortality (226,230). An experienced cardiac anesthetist with an understanding of Eisenmenger physiology should administer anesthesia. Eisenmenger patients are particularly vulnerable to alterations in hemodynamics induced by anesthesia or surgery such as minor decrease in systemic vascular resistance that can increase right-to-left shunting and possibly potentiate cardiovascular collapse. Local anesthesia should be used whenever possible. Avoidance of prolonged fasting and especially dehydration, the use of antibiotic prophylaxis when appropriate (231), and careful intraoperative monitoring (sometimes with an arterial line a central venous line to allow early detection of sudden pressure and volume changes during surgery) are recommended (230,232). The choice of general versus epidural-spinal anesthesia is controversial. An experienced cardiac anesthetist with an understanding of Eisenmenger physiology should administer anesthesia. Additional risks of surgery include excessive bleeding, postoperative arrhythmias, and deep venous thrombosis with paradoxic emboli. An "air filter" or "bubble trap" should be used for any intravenous lines. Early ambulation is recommended (230,232). Post-operative care in an ICU setting is optimal (233,234).
As a general rule, hemoptysis should lead to a chest x-ray and often CT scanning to look for pulmonary hemorrhage or secondary cause, a CBC, and a clinical decision as to whether the patient needs hospital admission. Bed rest should be implemented and, while usually self-limiting, each such episode should be regarded as potentially life-threatening. A treatable cause should be excluded although it is most commonly due to bleeding bronchial vessels or pulmonary infarction.
Transplant. Young age at presentation, recent worsening in functional class, history of syncope, right-sided failure and supraventricular arrhythmias are harbingers of poor prognosis and should accelerate the decision-making process regarding timing of transplantation (226,227,235).
Transplant. When patients are severely incapacitated from severe hypoxemia or congestive heart failure, the main intervention available is lung (plus repair of the cardiac defect) or heart-lung transplantation. This is generally reserved for those individuals without contraindications felt to have a one-year survival of less than 50%. Such assessment is fraught with difficulty because of the unpredictability of the time course of the disease and the risk of sudden death. The 1-year survival rate for adults undergoing lung transplantation with primary intracardiac repair is 70-80% with less than 50% of patients alive 4 years after transplantation (242-245). The outcome after heart-lung transplantation is no better with a 1-year survival rate of 60-80% and a 10-year survival rate of less than 30% (242,244). These options, however sobering, may be relatively attractive to individuals confronting death and having an intolerable quality of life.
Calcium channel blockers. The chronic use of nifedipine in a small group of patients with Eisenmenger syndrome demonstrated a small but significant increase in exercise tolerance (246) and a decrease in pulmonary vascular resistance, especially in children (247). This therapy is still considered investigational and should only be prescribed in a clinical research setting.
Angiotensin Converting Enzyme Inhibitors. Data available on a highly selected group of 10 patients with cyanotic congenital heart disease showed no change in oxygen saturation despite a subjective improvement in functional capacity (248). Proponents of the use of angiotensin converting enzyme inhibitors in these patients argue that by decreasing systemic vascular resistance one improves the cardiac output and thus oxygen delivery. The counter argument is that these agents are potentially dangerous because they lower systemic vascular resistance without changing pulmonary vascular resistance and lead to an increase in right-to-left shunting. The use of this medication remains highly experimental and again should only be administered within the boundaries of a study trial guided by rigorous monitoring.
Prostacyclin. A recent study of chronic prostacyclin administration in such patients showed improvement in hemodynamics (lower pulmonary vascular resistance and increased cardiac output) and a somewhat increased exercise capacity (249). Further research in this field is needed before recommendations on the use of prostaglandins in these patients can be made.
Pulmonary artery banding. Pulmonary artery banding in one acyanotic patient with biopsy-proven pulmonary vascular changes led to regression of pulmonary vascular changes which made surgical closure of the defects possible (250). Further data regarding this revolutionary practice is needed.
Section XVI - Management of Cyanotic Patients
Part I - Background Information
Cyanosis is a bluish discoloration of the skin and mucous membranes resulting from an increased amount of reduced hemoglobin. Central cyanosis in patients with congenital heart disease occurs when persistent venous to arterial mixing occurs secondary to a right to left shunt, resulting in chronic hypoxemia. In the presence of hypoxemia, adaptive mechanisms increase oxygen delivery. These include an increase in oxygen content, a rightward shift in the oxyhemoglobin dissociation curve and increase in cardiac output. Oxygen delivery is enhanced at the cost of a higher hematocrit as erythropoietin production is stimulated.
Cyanosis is observed in unoperated and palliated patients with cyanotic lesions. Cyanotic lesions are summarized below (Table 1) and palliative shunts aimed at increasing pulmonary blood flow are described in appendix VI (251,252).
Table 1: Cyanotic Lesions
Adult survival into the 7th decade, although rare, is documented in cyanotic patients (253,254). Survival is determined by two sets of factors: the underlying cardiac condition and its repercussion on the heart and pulmonary circulation; and the medical complications of cyanosis. When cyanosis is not relieved, chronic hypoxemia and erythrocytosis result in hematologic, neurologic, renal and rheumatic complications (255).
Hematologic complications of chronic hypoxemia include: erythrocytosis; iron deficiency and bleeding diathesis (256). Erythrocytosis is different from polycythemia which is the result of an increase in cellular mass not only of red cells, but also of white cells and platelets. Erythrocytosis may cause hyperviscosity symptoms, including headaches, faintness, dizziness, fatigue, altered mentation, visual disturbances, paresthesias, tinnitus and myalgias. Symptoms are classified as mild to moderate, when they interfere with only some activities, or they can be marked to severe, when they interfere with all or most activities. Individual patients will have the same symptoms each time they occur. They will be relieved by phlebotomy to an appropriate hematocrit level. In the iron-replete state, moderate to severe hyperviscosity symptoms may occur, typically when hematocrit levels are in excess of 65%.
Hemostatic abnormalities have been documented in cyanotic patients with erythrocytosis and can occur in up to 20% of patients. Bleeding tendency can be mild and superficial, leading to easy bruising, skin petechiae, mucosal bleeding, or can be moderate or life-threatening with epistaxis, hemoptysis, or postoperative bleeding (256). An elevated prothrombin and partial thromboplastin time, decreased levels of factors V, VII, VIII and IX in addition to thrombocytopenia, qualitative and quantitative platelet disorders have all been described. Findings analogous to type II von Willebrand's disease with absence of the largest vWF multimers are described. Hemostatic defects correlate with erythrocytosis. The management of bleeding diathesis is determined by the clinical circumstance, the severity and the abnormal hemostatic parameters.
Iron deficiency is a common finding in cyanotic adult patients occurring because of phlebotomy or excessive bleeding. Although normochromic erythrocytosis is not usually symptomatic at hematocrit levels of less than 65%, iron deficiency may manifest as symptoms similar to hyperviscosity at hematocrits well below 65% (259).
Neurologic complications including cerebral hemorrhage can occur secondary to hemostatic defects and can be seen following use of anticoagulant therapy. Patients with right-to-left shunts may be at risk for paradoxical cerebral emboli. Brain abscess should be suspected in a cyanotic patient with a new or different headache or any neurological symptoms (260,261). Attention should be paid to the use of air filters in peripheral/central lines to avoid paradoxical emboli through a right-to-left shunt.
Renal dysfunction can manifest itself as proteinuria, hyperuricemia, or renal failure (262). Increased blood viscosity from erythrocytosis in combination with arteriolar vasoconstriction can lead to renal hypoperfusion with progressive glomerulosclerosis. Hyperuricemia is common and is thought to be due mainly to the decreased reabsorption of uric acid rather than to overproduction from erythrocytosis. Urate nephropathy, uric acid nephrolithiasis and gouty arthritis are rare but may occur.
Rheumatologic complications include gout and hypertrophic osteoarthropathy which is thought to be responsible for the arthralgias and bone pain affecting up to a third of patients.
Gallstones composed of calcium bilirubinate and consequent cholecystitis occur with increased frequency in adults, adolescents and children.
An initial diagnostic work up should:
The diagnostic work-up should include:
Interventions have the goal of either prolonging life or improving symptoms. There exists controversy as to whether a cyanotic adult survivor who is stable, but eligible for complete physiologic repair, should be considered for surgery to improve or prolong life. Outcome varies widely and depends on the lesion and the surgical expertise and support. Symptomatic patients may manifest worsening cyanosis and ensuing medical complications, or decreasing functional capacity with or without the occurrence of symptomatic arrhythmias.
Percutaneous closure of intracardiac shunts. A variety of devices can be used to close ASDs, PDAs and occasionally VSDs (see previous sections I, II and IV).
Palliative surgical interventions performed in patients with cyanotic lesions are defined as those operations which serve to either increase or decrease pulmonary blood flow while allowing a mixed circulation and cyanosis to persist. Palliative surgical shunts aimed at increasing pulmonary blood flow are summarized in Table 2.
Physiologic repair is a term which can be applied to procedures which result in total or near-total anatomic and physiologic separation of the pulmonary and systemic circulations in complex cyanotic lesions thereby resulting in relief of cyanosis. These are described throughout this document with reference to specific lesions.
Transplantation of heart, one or both lungs with surgical shunt closure and heart-lung transplantation have been performed in cyanotic patients with or without palliation who are no longer candidates for other forms of intervention. Pulmonary vascular obstructive disease precludes isolated heart transplantation but an increasing number of patients with previous palliation and ventricular failure are successfully undergoing cardiac transplantation (264). Technical difficulties relate to previous thoracotomies and bleeding tendency in addition to intracardiac and pulmonary anatomic distortion from previous intervention.
Palliative surgical interventions. Systemic arterial-to-pulmonary artery shunts result in improved saturation levels with high levels of pulmonary blood flow (265,266). The long-term complications of these shunts may include pulmonary hypertension, pulmonary artery stenosis and volume overload of the systemic ventricle often making further surgical intervention more difficult or impossible. This is particularly true of large central shunts, the Potts shunt, and the Waterston anastomosis. Blalock-Taussig shunts result in more controlled pulmonary flow but may stenose over time and can distort the pulmonary artery anatomy (266). Pulmonary artery banding can lead to distortion of the pulmonary artery complicating later repair.
Transplantation. The results of cardiac transplantation in properly selected patients with congenital heart disease, with and without previous palliative surgery have improved in recent years (264). Lung transplantation (single or double) (267), with intracardiac repair can be effective in reducing pulmonary hypertension.
Patients with Eisenmenger syndrome are at risk for sudden cardiac death, the etiology of which remains poorly defined (268). Multiple factors including arrhythmias have been described. In cyanotic patients, arrhythmias can be supraventricular or ventricular. In patients with poor ventricular function, both are poorly tolerated. The presence of atrial flutter/fibrillation will increase the risk of paradoxical emboli and stroke. The choice of antiarrhythmic drugs are complicated by the presence of ventricular dysfunction and lung disease. In addition, there have been no drug trials in this patient population to determine possible pro-arrhythmic effects. The use of pacemakers to treat bradyarrhythmias, which are primary or secondary to antiarrhythmic therapy can be complicated by inadequate venous access. The decision to use anticoagulants in patients with cyanosis is complicated by the presence of bleeding diathesis, and difficulty obtaining a true measure of INR due to reduced plasma volume. The use of implantable defibrillators for symptomatic malignant ventricular arrhythmia has not been studied in this patient population.
Pregnancy in cyanotic congenital heart disease excluding Eisenmenger's reaction, results in a 32% incidence of maternal cardiovascular complications and a 37% incidence of prematurity. Pregnant women with an oxygen saturation greater than 85% fare better than women with an oxygen saturation less than 85% (269).
Warfarin use when combined with pregnancy may cause a fetopathy, especially if the warfarin dose is greater than 5 mg daily.
Levonorgestrel may be safe as an oral contraceptive in women with cyanotic congenital heart disease.
All cyanotic patients should be followed by an ACHD cardiologist and particular attention should be paid to:
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