Pathology and Pathogenesis
Although most individuals with chronic pulmonary thromboembolic disease are unaware of a past thromboembolic event and give no history of deep vein thrombosis, the origin of most cases of unresolved pulmonary emboli are from acute embolic episodes. Why some patients have unresolved emboli is not certain, but a variety of factors must play a role, alone or in combination.
The volume of acute embolic material may simply overwhelm the lytic mechanisms. Total occlusion of a major arterial branch may prevent lytic material from reaching, and therefore dissolving, the embolus completely. Repetitive emboli may not be able to be resolved. The emboli may be made of substances that cannot be resolved by normal mechanisms (already well-organized fibrous thrombus, fat, or tumor). The lytic mechanisms themselves may be abnormal, or some patients may actually have a propensity for thrombus or a hypercoagulable state. In addition, there are other special circumstances. Chronic indwelling central venous catheters and pacemaker leads are sometimes associated with pulmonary emboli. More rare causes include tumor emboli; tumor fragments from stomach, breast, and kidney malignancies have been demonstrated to cause chronic pulmonary arterial occlusion. Right atrial myxomas may also fragment and embolize.
After the clot becomes wedged in the pulmonary artery, one of two processes occurs:82
Organization of the clot proceeds to canalization, producing multiple small endothelialized channels separated by fibrous septa (ie, bands and webs) or
Complete fibrous organization of the fibrin clot without canalization may result, leading to a solid mass of dense fibrous connective tissue totally obstructing the arterial lumen.
As previously described and discussed, in addition to the embolic material, a propensity for thrombosis or a hypercoagulable state may be present in a few patients. This abnormality may result in spontaneous thrombosis within the pulmonary vascular bed, encourage embolization, or be responsible for proximal propagation of thrombus after an embolus. But, whatever the predisposing factors to residual thrombus within the vessels, the final genesis of the resultant pulmonary vascular hypertension may be complex. With the passage of time, the increased pressure and flow as a result of redirected pulmonary blood flow in the previously normal pulmonary vascular bed can create a vasculopathy in the small precapillary blood vessels similar to the Eisenmenger's syndrome.
Factors other than the simple hemodynamic consequences of redirected blood flow are probably also involved in this process. For example, after a pneumonectomy, 100% of the right ventricular output flows to one lung, yet little increase in pulmonary pressure occurs, even with follow-up to 11 years.83 In patients with thromboembolic disease, however, we frequently detect pulmonary hypertension even when less than 50% of the vascular bed is occluded by thrombus. It thus appears that sympathetic neural connections, hormonal changes or both might initiate pulmonary hypertension in the initially unaffected pulmonary vascular bed. This process can occur with the initial occlusion either being in the same or the contralateral lung.
Regardless of the cause, the evolution of pulmonary hypertension as a result of changes in the previously unobstructed bed is serious, because this process may lead to an inoperable situation. Consequently, with our accumulating experience in patients with thrombotic pulmonary hypertension, we have increasingly been inclined toward early operation so as to avoid these changes.
To ensure accurate diagnosis in patients with chronic pulmonary thromboembolism, a standardized evaluation is recommended for all patients who present with unexplained pulmonary hypertension. This workup includes a chest radiograph, which may show either apparent vessel cutoffs of the lobar or segmental pulmonary arteries or regions, or oligemia suggesting vascular occlusion. The central pulmonary arteries are enlarged, and the right ventricle may also be enlarged without enlargement of the left atrium or ventricle (Fig. 55-5). Despite these classic findings, many patients present with a relatively normal chest radiograph, even in the setting of high degrees of pulmonary hypertension. The electrocardiogram demonstrates findings of right ventricular hypertrophy (right axis deviation, dominant R-wave in V1). Pulmonary function tests are necessary to exclude obstructive or restrictive intrinsic pulmonary parenchymal disease as the cause of pulmonary hypertension.
Chest radiograph of a patient with chronic thromboembolic pulmonary disease, and evidence of pulmonary hypertension. Note the enlarged right atrium and right ventricle, disparity of size between the left and right pulmonary arteries, and the hypoperfusion in several areas of the lung fields.
The ventilation-perfusion lung scan is the essential test for establishing the diagnosis of unresolved pulmonary thromboembolism. An entirely normal lung scan excludes the diagnosis of both acute or chronic, unresolved thromboembolism. The usual lung scan pattern in most patients with pulmonary hypertension either is relatively normal or shows a diffuse nonuniform perfusion.84,85–87 When subsegmental or larger perfusion defects are noted on the scan, even when matched with ventilatory defects, pulmonary angiography is appropriate to confirm or rule out thromboembolic disease.
Currently, pulmonary angiography still remains the gold standard for the diagnosis of CTEPH. Organized thromboembolic lesions do not have the appearance of the intravascular filling defects seen with acute pulmonary emboli, and experience is essential for the proper interpretation of pulmonary angiograms in patients with unresolved, chronic embolic disease. Organized thrombi appear as unusual filling defects, webs, or bands, or completely thrombosed vessels that may resemble congenital absence of the vessel87 (Fig. 55-6). Organized material along the wall of a re-canalized vessel produces a scalloped or serrated luminal edge. Because of both vessel-wall thickening and dilatation of proximal vessels, the contrast-filled lumen may appear relatively normal in diameter. Distal vessels demonstrate the rapid tapering and pruning characteristic of pulmonary hypertension (see Fig. 55-6).
Right and left pulmonary angiograms demonstrate enlarged pulmonary arteries, poststenotic dilatation of vessels, lack of filling to the periphery in many areas, and abrupt cutoffs of branches. The arrow points to intraluminal filling defects representative of a web or band.
Pulmonary angiography should be performed whenever there is a possibility that chronic thromboembolism is the etiology of pulmonary hypertension. Several thousand angiograms in pulmonary hypertensive patients have now been performed at our institution without mortality.
In addition to pulmonary angiography, patients over 40 undergo coronary arteriography and other cardiac investigation as necessary. If significant disease is found, additional cardiac surgery is performed at the time of pulmonary thromboendarterectomy.
In approximately 15% of cases, the differential diagnosis between primary pulmonary hypertension and distal and small vessel pulmonary thromboembolic disease remains unclear and hard to establish. In these patients, pulmonary angioscopy may be helpful. The pulmonary angioscope is a fiberoptic telescope that is placed through a central line into the pulmonary artery. The tip contains a balloon that is then filled with saline and pushed against the vessel wall. A bloodless field can thus be obtained to view the pulmonary artery wall. The classic appearance of chronic pulmonary thromboembolic disease by angioscopy consists of intimal thickening, with intimal irregularity and scarring, and webs across small vessels. These webs are thought to be the residue of resolved occluding thrombi of small vessels, but are important diagnostic findings. The presence of embolic disease as seen by occlusion of vessels, or the presence of thrombotic material is also diagnostic.
Although there were previous attempts, Allison90 did the first successful pulmonary "thromboendarterectomy" through a sternotomy using surface hypothermia, but only fresh clots were removed. Since then, there have been many occasional surgical reports of the surgical treatment of chronic pulmonary thromboembolism,91–94 but most of the surgical experience in pulmonary endarterectomy has been reported from the UCSD Medical Center. Braunwald commenced the UCSD experience with this operation in 1970, which now totals more than 2500 cases. The operation described in the following, using deep hypothermia and circulatory arrest, is the standard procedure.
When the diagnosis of thromboembolic pulmonary hypertension has been firmly established, the decision for operation is based on the severity of symptoms and the general condition of the patient. Early in the pulmonary endarterectomy experience, Moser and colleagues92 pointed out that there were three major reasons for considering thromboendarterectomy: hemodynamic, alveolo-respiratory, and prophylactic. The hemodynamic goal is to prevent or ameliorate right ventricular compromise caused by pulmonary hypertension. The respiratory objective is to improve respiratory function by the removal of a large ventilated but unperfused physiologic dead space, regardless of the severity of pulmonary hypertension. The prophylactic goal is to prevent progressive right ventricular dysfunction or retrograde extension of the obstruction, which might result in further cardiorespiratory deterioration or death.92 Our subsequent experience has added another prophylactic goal: the prevention of secondary arteriopathic changes in the remaining patent vessels.87
Most patients who undergo operation are within New York Heart Association (NYHA) class III or class IV. The ages of the patients in our series have ranged from 7 to 85 years. A typical patient will have a severely elevated PVR level at rest, the absence of significant comorbid disease unrelated to right heart failure, and the appearances of chronic thrombi on angiogram that appear to be relatively in balance with the measured PVR level. Exceptions to this general rule, of course, occur.
Although most patients have a PVR level in the range of 800 dynes/sec/cm-5 and pulmonary artery pressures less than systemic, the hypertrophy of the right ventricle that occurs over time makes pulmonary hypertension to suprasystemic levels possible. Therefore many patients (approximately 20% in our practice) have a level of PVR in excess of 1000 dynes/sec/cm–5 and suprasystemic pulmonary artery pressures. There is no upper limit of PVR level, pulmonary artery pressure, or degree of right ventricular dysfunction that excludes patients from operation.
We have become increasingly aware of the changes that can occur in the remaining patent (unaffected by clot) pulmonary vascular bed subjected to the higher pressures and flow that result from obstruction in other areas. Therefore, with the increasing experience and safety of the operation, we are tending to offer surgery to symptomatic patients whenever the angiogram demonstrates thromboembolic disease. A rare patient might have a PVR level that is normal at rest, although elevated with minimal exercise. This is usually a young patient with total unilateral pulmonary artery occlusion and unacceptable exertional dyspnea because of an elevation in dead space ventilation. Operation in this circumstance is performed not only to reperfuse lung tissue, but to re-establish a more normal ventilation perfusion relationship (thereby reducing minute ventilatory requirements during rest and exercise), and also to preserve the integrity of the contralateral circulation and prevent the chronic arterial changes associated with long-term exposure to pulmonary hypertension.
If not previously implanted, an inferior vena caval filter is routinely placed several days in advance of the operation.
There are several guiding principles for the operation. Surgical treatment and endarterectomy must be bilateral because this is a bilateral disease in the vast majority of our patients, and for pulmonary hypertension to be a major factor, both pulmonary vasculatures must be substantially involved. The only reasonable approach to both pulmonary arteries is therefore through a median sternotomy incision. Historically, there were many reports of unilateral operation, and occasionally this is still performed, in inexperienced centers, through a thoracotomy. However, the unilateral approach ignores the disease on the contralateral side, subjects the patient to hemodynamic jeopardy during the clamping of the pulmonary artery, does not allow good visibility because of the continued presence of bronchial blood flow, and exposes the patient to a repeat operation on the contralateral side. In addition, collateral channels develop in chronic thrombotic hypertension not only through the bronchial arteries but also from diaphragmatic, intercostal, and pleural vessels. The dissection of the lung in the pleural space via a thoracotomy incision can therefore be extremely bloody. The median sternotomy incision, apart from providing bilateral access, avoids entry into the pleural cavities, and allows the ready institution of cardiopulmonary bypass.
Cardiopulmonary bypass is essential to ensure cardiovascular stability when the operation is performed and cool the patient to allow circulatory arrest. Excellent visibility is required, in a bloodless field, to define an adequate endarterectomy plane and then follow the pulmonary endarterectomy specimen deep into the subsegmental vessels. Because of the copious bronchial blood flow usually present in these cases, periods of circulatory arrest are necessary to ensure perfect visibility. Again, there have been sporadic reports of the performance of this operation without circulatory arrest. However, it should be emphasized that although endarterectomy is possible without circulatory arrest, a complete endarterectomy is not. We always initiate the procedure without circulatory arrest, and a variable amount of dissection is possible before the circulation is stopped, but never complete dissection. The circulatory arrest periods are limited to 20 minutes, with restoration of flow between each arrest. With experience, the endarterectomy usually can be performed with a single period of circulatory arrest on each side.
A true endarterectomy in the plane of the media must be accomplished. It is essential to appreciate that the removal of visible thrombus is largely incidental to this operation. Indeed, in most patients, no free thrombus is present; and on initial direct examination, the pulmonary vascular bed may appear normal. The early literature on this procedure indicates that thrombectomy was often performed without endarterectomy, and in these cases the pulmonary artery pressures did not improve, often with the resultant death of the patient.
Preparation and Anesthetic Considerations
Much of the preoperative preparation is common to any open-heart procedure. Routine monitoring for anesthetic induction includes a surface electrocardiogram, cutaneous oximetry, and radial and pulmonary artery pressures. After anesthetic induction a femoral artery catheter, in addition to a radial arterial line, is also placed. This provides more accurate measurements during rewarming and on discontinuation of cardiopulmonary bypass because of the peripheral vasoconstriction that occurs after hypothermic circulatory arrest. It is generally removed in the intensive care unit when the two readings correlate.
Electroencephalographic recording is performed to ensure the absence of cerebral activity before circulatory arrest is induced. The patient's head is enveloped in a cooling jacket, and cerebral cooling is begun after the initiation of bypass. Temperature measurements are made of the esophagus, tympanic membrane, urinary catheter, rectum, and blood (through the Swan-Ganz catheter). If the patient's condition is stable after the induction of anesthesia, up to 500 mL of autologous whole blood is withdrawn for later use, and the volume deficit is replaced with crystalloid solution.
After a median sternotomy incision, the pericardium is incised longitudinally and attached to the wound edges. Typically the right heart is enlarged, with a tense right atrium and a variable degree of tricuspid regurgitation. There is usually severe right ventricular hypertrophy, and with critical degrees of obstruction, the patient's condition may become unstable with the manipulation of the heart.
Anticoagulation with heparin (400 U/kg, intravenously) is administered to prolong the activated clotting time beyond 400 seconds. Full cardiopulmonary bypass is instituted with high ascending aortic cannulation and two caval cannulae. These cannulae must be inserted into the superior and inferior vena cavae sufficiently to enable subsequent opening of the right atrium if necessary. A temporary pulmonary artery vent is placed in the midline of the main pulmonary artery 1 cm distal to the pulmonary valve. This will mark the beginning of the left pulmonary arteriotomy.
After cardiopulmonary bypass is initiated, surface cooling with both the head jacket and the cooling blanket is begun. The blood is cooled with the pump-oxygenator. During cooling a 10°C gradient between arterial blood and bladder or rectal temperature is maintained.93 Cooling generally takes 45 minutes to an hour. When ventricular fibrillation occurs, an additional vent is placed in the left atrium through the right superior pulmonary vein to prevent distention from the large amount of bronchial arterial blood flow that is common with these patients.
It is most convenient for the primary surgeon to stand initially on the patient's left side. During the cooling period, some preliminary dissection can be performed, with full mobilization of the right pulmonary artery from the ascending aorta. The superior vena cava is also fully mobilized. The approach to the right pulmonary artery is made medial, not lateral, to the superior vena cava. All dissection of the pulmonary arteries takes place intrapericardially, and neither pleural cavity should be entered. An incision is then made in the right pulmonary artery from beneath the ascending aorta out under the superior vena cava and entering the lower lobe branch of the pulmonary artery just after the take-off of the middle lobe artery (Fig. 55-7). The incision stays in the center of the vessel and continues into the lower rather than the middle lobe artery.
Recommended surgical approach on the right side. This approach, medial to the superior vena cava (SVC), between the superior vena cava and aorta, provides a direct view into the right pulmonary artery. Note that an approach on the lateral side of the superior vena cava will only provide a restricted view, and should be avoided.
Any loose thrombus, if present, is now removed, to obtain good visualization. It is most important to recognize, however, that first, an embolectomy without subsequent endarterectomy is quite ineffective and, second, that in most patients with chronic thromboembolic hypertension, direct examination of the pulmonary vascular bed at operation generally shows no obvious embolic material. Therefore, to the inexperienced or cursory glance, the pulmonary vascular bed may well appear normal even in patients with severe chronic embolic pulmonary hypertension.
If the bronchial circulation is not excessive, the endarterectomy plane can be found during this early dissection. However, although a small amount of dissection can be performed before the initiation of circulatory arrest, it is unwise to proceed unless perfect visibility is obtained because the development of a correct plane is essential.
There are four broad types of pulmonary occlusive disease related to thrombus that can be appreciated, and we use the following classification87,94: Type I disease (approximately 10% of cases of thromboembolic pulmonary hypertension) (Fig. 55-8) refers to the situation in which major vessel clot is present and readily visible on the opening of the pulmonary arteries. All central thrombotic material has to be completely removed before the endarterectomy. In type II disease (approximately 70% of cases; Fig. 55-9), no major vessel thrombus can be appreciated. In these cases only thickened intima can be seen, occasionally with webs, and the endarterectomy plane is raised in the main, lobar, or segmental vessels. Type III disease (approximately 20% of cases; Fig. 55-10) presents the most challenging surgical situation. The disease is very distal and confined to the segmental and subsegmental branches. No occlusion of vessels can be seen initially. The endarterectomy plane must be carefully and painstakingly raised in each segmental and subsegmental branch. Type III disease is most often associated with presumed repetitive thrombi from indwelling catheters (such as pacemaker wires) or ventriculo-atrial shunts. Type IV disease (Fig. 55-11) does not represent primary thromboembolic pulmonary hypertension and is inoperable. In this entity there is intrinsic small vessel disease, although secondary thrombus may occur as a result of stasis. Small-vessel disease may be unrelated to thromboembolic events ("primary" pulmonary hypertension) or occur in relation to thromboembolic hypertension as a result of a high flow or high pressure state in previously unaffected vessels similar to the generation of Eisenmenger's syndrome. We believe that there may also be sympathetic "cross-talk" from an affected contralateral side or stenotic areas in the same lung.
Surgical specimen removed from a patient showing evidence of some fresh and some old thrombus in the main and both right and left pulmonary arteries. Note that simple removal of the gross disease initially encountered on pulmonary arteriotomy will not be therapeutic, and any meaningful outcome involves a full endarterectomy into all the distal segments.
Specimen removed in a patient with type II disease. Both pulmonary arteries have evidence of chronic thromboembolic material. Note the distal tails of the specimen in each branch. Full resolution of pulmonary hypertension is dependent on complete removal of all the distal tails.
Specimen removed from a patient with type III disease. Note that the disease is distal, and the plane was raised at each segmental level.
Note the absence of distal "tails" in this specimen removed from a patient with surgical classification type IV. All "tails" are replaced by "trousers". No clinical benefit was obtained from this procedure and the patient's postoperative hemodynamics were not improved, despite what appears to be an impressive endarterectomy specimen. The patient had primary pulmonary hypertension.
When the patient's temperature reaches 20°C, the aorta is cross-clamped and a single dose of cold cardioplegic solution (I L) is administered. Additional myocardial protection is obtained by the use of a cooling jacket. The entire procedure is now performed with a single aortic cross-clamp period with no further administration of cardioplegic solution.
A modified cerebellar retractor is placed between the aorta and superior vena cava. When blood obscures direct vision of the pulmonary vascular bed, thiopental is administered (500 mg to 1 g) until the electroencephalogram becomes isoelectric. Circulatory arrest is then initiated, and the patient is exsanguinated. All monitoring lines to the patient are turned off to prevent the aspiration of air. Snares are tightened around the cannulae in the superior and inferior vena cavae. It is rare that one 20-minute period for each side is exceeded. Although retrograde cerebral perfusion has been advocated for total circulatory arrest in other procedures, it is not helpful in this operation because it does not allow a completely bloodless field, and with the short arrest times that can be achieved with experience, it is not necessary.
Any residual loose, thrombotic debris encountered is removed. Then, a microtome knife is used to develop the endarterectomy plane posteriorly, because any inadvertent egress in this site could be repaired readily, or simply left alone. Dissection in the correct plane is critical because if the plane is too deep the pulmonary artery may perforate, with fatal results, and if the dissection plane is not deep enough, inadequate amounts of the chronically thromboembolic material will be removed. The plane should only be sought in the diseased parts of the artery; this often requires the initial dissection to begin quite distally.
The ideal layer is marked with a pearly white plane, which strips easily. There should be no residual yellow plaque. If the dissection is too deep, a reddish or pinkish color indicates the adventitia has been reached. A more superficial plane should be sought immediately.
Once the plane is correctly developed, a full-thickness layer is left in the region of the incision to ease subsequent repair. The endarterectomy is then performed with an eversion technique, using a specially developed dissection instrument (Jamieson aspirator, Fehling Corp.). Because the vessel is partly everted and subsegmental branches are being worked on, a perforation here will become completely inaccessible and invisible later. This is why absolute visualization in a completely bloodless field provided by circulatory arrest is essential. It is important that each subsegmental branch is followed and freed individually until it ends in a "tail," beyond which there is no further obstruction.
Once the right-sided endarterectomy is completed, circulation is restarted, and the arteriotomy is repaired with a continuous 6-0 polypropylene suture. The hemostatic nature of this closure is aided by the nature of the initial dissection, with the full thickness of the pulmonary artery being preserved immediately adjacent to the incision.
The surgeon now moves to the patient's right side. The pulmonary vent catheter is withdrawn, and an arteriotomy is made from the site of the pulmonary vent hole laterally beneath the pericardial reflection, and again into the lower lobe, but avoiding entry into the left pleural space. Additional lateral dissection does not enhance intraluminal visibility, may endanger the left phrenic nerve, and makes subsequent repair of the left pulmonary artery more difficult (Fig. 55-12). There is often a lymphatic vessel encountered on the left pulmonary artery at the level of the pericardial reflection, and it is wise to clip this before it being divided with the pulmonary artery incision.
Surgical approach on the left side. The incision in the left pulmonary artery begins in the midpoint of the main pulmonary trunk, at the insertion site of the pulmonary artery vent. This incision provides better visibility than a more distal approach (dotted line and arrow). Care must be taken to avoid injury to the phrenic nerve.
The left-sided dissection is virtually analogous in all respects to that accomplished on the right. By the time the circulation is arrested once more it will have been reinitiated for at least 10 minutes, by which time the venous oxygen saturations are in excess of 90%. The duration of circulatory arrest intervals are again limited to 20 minutes.
After the completion of the endarterectomy, cardiopulmonary bypass is reinstituted and warming is commenced. Methylprednisolone (500 mg, intravenously) and mannitol (12.5 g, intravenously) are administered, and during warming a 10°C temperature gradient is maintained between the perfusate and body temperature, with a maximum perfusate temperature of 37°C. If the systemic vascular resistance level is high, nitroprusside is administered to promote vasodilatation and warming. The rewarming period generally takes approximately 90 to 120 minutes but varies according to the body mass of the patient.
When the left pulmonary arteriotomy has been repaired, the pulmonary artery vent is replaced at the top of the incision. The right atrium is then opened and examined. Any intra-atrial communication is closed. Although tricuspid valve regurgitation is invariable in these patients and is often severe, tricuspid valve repair is not performed unless there is independent structural damage to the tricuspid valve itself. Right ventricular remodeling occurs within a few days, with the return of tricuspid competence. If other cardiac procedures are required, such as coronary artery or mitral or aortic valve surgery, these are conveniently performed during the systemic rewarming period. Myocardial cooling is discontinued once all cardiac procedures have been concluded. The left atrial vent is removed, and the vent site is repaired. All air is removed from the heart, and the aortic cross-clamp is removed.
When the patient has rewarmed, cardiopulmonary bypass is discontinued. Dopamine hydrochloride is routinely administered at renal doses, and other inotropic agents and vasodilators are titrated as necessary to sustain acceptable hemodynamics. The cardiac output is generally high, with a low systemic vascular resistance. Temporary pacing wires are placed.
Despite the duration of extracorporeal circulation, hemostasis is readily achieved, and blood products are generally unnecessary. Wound closure is routine. A vigorous diuresis is usual for the next few hours, also a result of the previous systemic hypothermia.
Meticulous postoperative management is essential to the success of this operation. All patients are mechanically ventilated overnight, and subjected to a maintained diuresis with the goal of reaching the patient's preoperative weight within 24 hours. Although much of the postoperative care is common to more ordinary open-heart surgery patients, there are some important differences.
A higher minute ventilation is often required early after the operation to compensate for the temporary metabolic acidosis that develops after the long period of circulatory arrest, hypothermia, and cardiopulmonary bypass. Tidal volumes higher than those normally recommended after cardiac surgery are therefore generally used to obtain optimal gas exchange. The maximum inspiratory pressure is maintained below 30 cm of water if possible. Extubation should be performed on the first postoperative day, whenever possible.
Patients have considerable positive fluid balance after operation. After hypothermic circulatory arrest, patients initiate an early spontaneous aggressive diuresis for unknown reasons, but this may in part be related to the increased cardiac output related to a now lower PVR level, and improved RV function. This diuresis should be augmented with diuretics, however, with the aim of returning the patient to the preoperative fluid balance within 24 hours of operation. Because of the increased cardiac output, some degree of systemic hypotension is readily tolerated. Fluid administration is minimized, and the patient's hematocrit level should be maintained above 30% to increase oxygen-carrying capacity and to reduce the likelihood of the pulmonary reperfusion phenomenon.
The development of atrial arrhythmias, at approximately 10%, is no more common than that encountered in patients who undergo other types of non–valvular heart surgery. When a small atrial septal defect or persistent foramen ovale is closed this is done with a small inferior atrial incision directly over the fossa ovalis, away from the conduction system of the atrium or its blood supply. The siting and size of this incision may be helpful in the reduction of the incidence of these arrhythmias.
Despite the requirement for the maintenance of an adequate hematocrit level, with careful blood conservation techniques used during operation, transfusion is required in a minority of patients.
Inferior Vena Caval Filter and Anticoagulation
A Greenfield filter is usually inserted before operation, to minimize recurrent pulmonary embolism after pulmonary endarterectomy. However, if this is not possible, it can also be inserted at the time of operation. If the device is to be placed at operation, radiopaque markers should be placed over the level of the spine corresponding to the location of the renal veins to allow correct positioning. Postoperative venous thrombosis prophylaxis with intermittent pneumatic compression devices is used, and the use of subcutaneous heparin is begun on the evening of surgery. Anticoagulation with warfarin is begun as soon as the pacing wires and mediastinal drainage tubes are removed, with a target international normalized ratio of 2.5 to 3.
Aside from complications that are associated with open heart and major lung surgery (arrhythmias, atelectasis, wound infection, pneumonia, mediastinal bleeding, etc.), there are complications specific to this operation. These include persistent pulmonary hypertension, reperfusion pulmonary response, and neurologic disorders related to deep hypothermia.
Persistent Pulmonary Hypertension
The decrease in PVR level usually results in an immediate and sustained restoration of pulmonary artery pressures to normal levels, with a marked increase in cardiac output. In a few patients, an immediately normal pulmonary vascular tone is not achieved, but an additional substantial reduction may occur over the next few days because of the subsequent relaxation of small vessels and the resolution of intraoperative factors such as pulmonary edema. In such patients, it is usual to see a large pulmonary artery pulse pressure, the low diastolic pressure indicating good runoff, yet persistent pulmonary arterial inflexibility still resulting in a high systolic pressure.
There are a few patients in whom the pulmonary artery pressures do not resolve substantially. If the operation has been performed as described in the preceding, using circulatory arrest, and ensuring that all distal disease is removed, this will be the result of type IV disease. We do operate on some patients with severe pulmonary hypertension but equivocal embolic disease. Despite the considerable risk of attempted endarterectomy in these patients, because transplantation is the only other avenue of therapy, there may be a point when it is unlikely that a patient will survive until a donor is found. In our most recent 500 patients, the majority of perioperative deaths were directly attributable to the problem of inadequate relief of pulmonary artery hypertension. This was a diagnostic rather than an operative technical problem. Attempts at pharmacologic manipulation of high residual PVR levels with sodium nitroprusside, epoprostenol sodium, or inhaled nitric oxide are generally not effective. Because the residual hypertensive defect is fixed, it is not appropriate to use mechanical circulatory support or extracorporeal membrane oxygenation in these patients if they deteriorate subsequently.
The "Reperfusion Response"
A specific complication that occurs in most patients to some degree is localized pulmonary edema, or the "reperfusion response." Reperfusion response or reperfusion injury is defined as a radiologic opacity seen in the lungs within 72 hours of pulmonary endarterectomy. This unfortunately loose definition may therefore encompass many causes, such as fluid overload and infection.
True reperfusion injury that directly adversely impacts the clinical course of the patient now occurs in approximately 10% of patients. In its most dramatic form, it occurs soon after operation (within a few hours) and is associated with profound desaturation. Edema-like fluid, sometimes with a bloody tinge, is suctioned from the endotracheal tube.95 Frank blood from the endotracheal tube, however, signifies a mechanical violation of the blood airway barrier that has occurred at operation and generally stems from a technical error, though we have seen two cases where significant blood in the airway was the result of a technically good operation, but reperfusion of a known infarcted area of the lung. This complication should be managed, if possible, by identification of the affected area by bronchoscopy and balloon occlusion of the affected lobe until coagulation can be normalized.
One common cause of reperfusion pulmonary edema is persistent high pulmonary artery pressures after operation when a thorough endarterectomy has been performed in certain areas, but there remains a large part of the pulmonary vascular bed affected by type IV change. However, the reperfusion phenomenon is often encountered in patients after a seemingly technically perfect operation with complete resolution of high pulmonary artery pressures. In these cases the response may be one of reactive hyperemia, after the revascularization of segments of the pulmonary arterial bed that have long experienced no flow. Other contributing factors may include perioperative pulmonary ischemia and conditions associated with high permeability lung injury in the area of the now denuded endothelium. Fortunately, the incidence of this complication is much less common now in our series, probably as a result of the more complete and expeditious removal of the endarterectomy specimen that has come with the large experience over the last decade.
Management of the "Reperfusion Response"
Early measures should be taken to minimize the development of pulmonary edema with diuresis, maintenance of hematocrit levels, and the early use of peak end-expiratory pressure. Once the capillary leak has been established, treatment is supportive because reperfusion pulmonary edema will eventually resolve if satisfactory hemodynamics and oxygenation can be maintained. Careful management of ventilation and fluid balance is required. The hematocrit is kept high (32 to 36%), and the patient undergoes aggressive diuresis, even if this requires ultrafiltration. The patient's ventilatory status may be dramatically position sensitive. The Fio2 level is kept as low as is compatible with an oxygen saturation of 90%. A careful titration of positive end-expiratory pressure is carried out, with a progressive transition from volume- to pressure-limited inverse ratio ventilation and the acceptance of moderate hypercapnia.95 The use of steroids is discouraged because they are generally ineffective and may lead to infection. Infrequently, inhaled nitric oxide at 20 to 40 parts per million can improve the gas exchange. On occasion we have used extracorporeal perfusion support (extracorporeal membrane oxygenator or extracorporeal carbon dioxide removal) until ventilation can be resumed satisfactorily, usually after 7 to 10 days. However the use of this support is limited to patients who have benefited from hemodynamic improvement, but are suffering from significant reperfusion response. Extracorporeal devices should not be used if there is no evidence or hope of subsequent hemodynamic improvement, because it will not play a role in improving irreversible pulmonary pressures and carries mortality close to 100%.
Early in the pulmonary endarterectomy experience (before 1990), there was a substantial incidence of postoperative delirium. A study of 28 patients who underwent pulmonary endarterectomy showed that 77% experienced the development of this complication.96,97 Delirium appeared to be related to an accumulated duration of circulatory arrest time of more than 55 minutes; the incidence fell to 11% with significantly shorter periods of arrest time.96–98 With the more expeditious operation that has come with our increased experience, postoperative confusion is now encountered no more commonly than with ordinary open heart surgery.
More than 2700 pulmonary thromboendarterectomy have been performed at UCSD Medical Center since 1970. Most of these cases (more than 2600) have been completed since 1990, when the surgical procedure was modified as described earlier in this chapter. The mean patient age in our group is about 52 years, with a range of 7 to 85 years. There is a very slight male predominance. In nearly one-third of the cases, at least one additional cardiac procedure was performed at the time of operation. Most commonly, the adjunct procedure was closure of a persistent foramen ovale or atrial septal defect (26%) or coronary artery bypass grafting (8%).87
A reduction in pulmonary pressures and resistance to normal levels and a corresponding improvement in pulmonary blood flow and cardiac output are generally immediate and sustained.98,99 In general, these changes can be assumed to be permanent. Whereas before the operation, more than 95% of the patients are in NYHA functional class III or IV; at 1 year after the operation, 95% of patients remain in NYHA functional class I or II.99,100 In addition, echocardiographic studies have demonstrated that, with the elimination of chronic pressure overload, right ventricular geometry rapidly reverts toward normal. Right atrial and right ventricular enlargement regresses. Tricuspid valve function returns to normal within a few days as a result of restoration of tricuspid annular geometry after the remodeling of the right ventricle, and tricuspid repair is not therefore part of the operation.
Severe reperfusion injury was the single most frequent complication in the UCSD series, occurring in 10% of patients. Some of these patients did not survive, and other patients required prolonged mechanical ventilatory support. A few patients were salvaged only by the use of extracorporeal support and blood carbon dioxide removal. Neurologic complications from circulatory arrest appear to have been eliminated, probably as a result of the shorter circulatory arrest periods now experienced, and perioperative confusion and stroke are now no more frequent than with conventional open heart surgery. Early postoperative hemorrhage required re-exploration in 2.5% of patients, and less than half of patients required intraoperative or postoperative blood transfusion. Despite the prolonged operation, wound infections are relatively infrequent. Only 1.8% experienced the development of sternal wound complications, including sterile dehiscence or mediastinitis.
In our experience, the overall mortality rate (30 days or in-hospital if the hospital course is prolonged) is about 7% for the entire patient group, which encompasses a time span of over 35 years. The mortality rate was 9.4% in 1989 and has been less than 6% for the more than 2400 patients who have undergone the operation since 1990. In our most recent experience over the last 5 years, the mortality rate has been less than 4%. With our increasing experience and many referrals, we continue to accept some patients who, in retrospect, were unsuitable candidates for the procedure (type IV disease). We also accept patients in whom we know that the entire degree of pulmonary hypertension cannot be explained by the occlusive disease detected by angiography but feel that they will be benefited by operation, albeit at higher risk. Residual causes of death are operation on patients in whom thromboembolic disease was not the cause of the pulmonary hypertension (50%) and the rare case of reperfusion pulmonary edema that progresses to a respiratory distress syndrome of long standing, which is not reversible (25%).
A survey of the surviving patients who underwent pulmonary endarterectomy surgery at UCSD between 1970 and 1995 formally evaluated the long-term outcome.100 Questionnaires were mailed to 420 patients who were more than 1 year after operation. Responses were obtained from 308 patients. Survival, functional status, quality of life, and the subsequent use of medical help were assessed. Survival after pulmonary thromboendarterectomy was 75% at 6 years or more. Ninety-three percent of the patients were found to be in NYHA Class I or II, compared with about 95% of the patients being in NYHA Class III or IV preoperatively. Of the working population, 62% of patients who were unemployed before operation returned to work. Patients who had undergone pulmonary endarterectomy scored several quality-of-life components just slightly lower than normal individuals, but significantly higher than the patients before endarterectomy. Only 10% of patients used oxygen, and in response to the question, "How do you feel about the quality of your life since your surgery?" Seventy-seven percent replied much improved, and twenty percent replied improved. These data appear to confirm that pulmonary endarterectomy offers substantial improvement in survival, function, and quality of life, with minimal later health-care requirements.100