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Ann Thorac Surg 2001;72:13-18
© 2001 The Society of Thoracic Surgeons

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Original article: cardiovascular

Pulmonary thromboendarterectomy combined with other cardiac operations: indications, surgical approach, and outcome

Address reprint requests to Dr Thistlethwaite, Division of Cardiothoracic Surgery, University of California, San Diego, 200 West Arbor Dr, San Diego, CA 92103-8892
e-mail: pthistlethwaite{at}ucsd.edu

Presented at the Thirty-seventh Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 29–31, 2001.

	Abstract

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Background. Patients with pulmonary hypertension due to chronic thromboembolic disease benefit from pulmonary thromboendarterectomy. A subset of these patients present with concomitant coronary or valvular disease.

Methods. From July 1990 to July 2000, 90 patients (68 males, 22 females, mean age 68 years) with pulmonary vascular resistance (PVR) ranging from 297 to 2261 dynes · sec · cm^-5 underwent pulmonary thromboendarterectomy in conjunction with coronary bypass grafting (59 patients), coronary artery bypass grafting/foramen ovale closure (24 patients), tricuspid annuloplasty (3 patients), mitral valve repair (2 patients), and aortic valve replacement (2 patients). The perioperative and hemodynamic outcomes of these patients were compared with the cohort of 1,100 isolated pulmonary thromboendarterectomies performed at our institution during this time.

Results. Overall perioperative survival (93.3%; 84 of 90 patients) and mean diminution in PVR (521 dynes · sec · cm^-5) for patients undergoing combined operations were similar to those undergoing pulmonary thromboendarterectomy alone (94.2% survival; 1034 of 1100 patients; 547 dynes · sec · cm^-5 mean PVR reduction). Although patients undergoing combined operations were older (mean age 68 vs 50 years, p < 0.0001), had longer hospital stays (median 14 vs 9 days), and had worse left ventricular function (mean preoperative cardiac output 3.1 vs 4.4, p < 0.0001), there was no difference in cross-clamp time, resolution of tricuspid regurgitation, or postoperative systolic function between these two groups.

Conclusions. Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension may be performed safely in conjunction with other cardiac operations. Older patients evaluated for pulmonary thromboendarterectomy should be screened for concomitant coronary and valvular disease.

	Introduction

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Pulmonary hypertension resulting from chronic thromboembolic occlusive disease or recurrent unresolved pulmonary emboli is well known to be a poor prognostic factor for long-term survival and is a cause of significant patient morbidity [1]. In select patients, pulmonary thromboendarterectomy is an effective modality for treating proximal thromboembolic disease in the pulmonary artery tree [2]. We and others have shown that pulmonary thromboendarterectomy ameliorates pulmonary hypertension by improving lung ventilation-perfusion match, arresting right ventricular dysfunction, limiting retrograde extension of clot obstruction, and preventing arteriopathic changes in the remaining patent pulmonary vessels [3, 4].

A subset of patients with surgically accessible chronic thromboembolic disease present with concomitant coronary artery disease or valvular dysfunction. Previous studies have shown coronary artery bypass grafting in patients undergoing lung resection [5] or single lung transplantation [6] to be an important independent risk factor for short- and long-term mortality. Similarly, high pulmonary vascular resistance and elevated pulmonary artery pressures have been linked to decreased postoperative survival in coronary bypass patients [7]. Although clinical series have reported overall mortality for various combined heart and lung operations [8], none have addressed the results of coronary artery bypass surgery or valve repair/replacement in association with pulmonary thromboendarterectomy. The purpose of the current study was to compare hemodynamic results, perioperative morbidity, and 1-year survival within a large cohort of patients undergoing pulmonary thromboendarterectomy alone or in conjunction with other cardiac operations including coronary artery bypass grafting, aortic valve replacement, and mitral or tricuspid valve repair at the University of California, San Diego.

	Material and methods

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Patient population
Between July 1990 and July 2000, 1,100 patients (561 men and 539 women; mean age 50.4 years, range 24 to 82 years) underwent pulmonary thromboendarterectomy at the University of California, San Diego for pulmonary hypertension resulting from chronic thromboembolic disease. Thirty percent (330 patients) underwent simultaneous closure of a secondary foramen ovale, opened by elevated right atrial pressures. The selection criteria for pulmonary thromboendarterectomy patients included: (1) New York Heart Association (NYHA) class III or IV; (2) pulmonary vascular resistance greater than 290 dynes · sec · cm^-5; (3) absence of significant noncardiac comorbid disease, and (4) the appearance of chronic thrombi on pulmonary angiogram.

Ninety patients were retrospectively identified as having undergone a concomitant major cardiac operation at the time of pulmonary thromboendarterectomy. Of these, 59 patients (41 males, 18 females; mean age 67.4 years) underwent pulmonary thromboendarterectomy-coronary artery bypass grafting (PTE-CABG) with an average of 2.7 grafts per patient; 24 patients (19 males, 5 females; mean age 70.7 years) underwent pulmonary thromboendarterectomy-coronary artery bypass grafting-foramen ovale closure (PTE-CABG-PFO) with an average of 2.6 grafts per patient; 3 male patients (mean age 60.0 years) underwent pulmonary thromboendarterectomy-tricuspid valve repair (PTE-TV repair); 2 male patients (mean age 70.5 years) underwent pulmonary thromboendarterectomy-mitral valve repair (PTE-MV repair); and 2 male patients (mean age 70.5 years) underwent pulmonary thromboendarterectomy-mechanical aortic valve replacement (PTE-AVR). Of the 3 patients who underwent tricuspid annuloplasty, 2 had valvular endocarditis with annular vegetations and chordal destruction, while 1 had extensive atrial thrombus distorting and obstructing the valve. The 2 patients who had mitral valve repair had myxomatous valve pathology corrected by either anterior or posterior leaflet resection and posterior ring annuloplasty. Both patients with aortic valve pathology requiring valve replacement with a St. Jude prosthesis had valvular calcific degeneration. All patients undergoing combined operations were in New York Heart Association class III or IV. According to the usual practice at our institution, all patients underwent transthoracic echocardiography and preoperative pulmonary angiography. Greenfield vena caval filters were placed in all patients before surgery since 1989.

Operative techniques
All pulmonary thromboendarterectomy operations were performed through a median sternotomy. After initiation of cardiopulmonary bypass, during systemic cooling to 20°C, the right pulmonary artery was mobilized intrapericardially from the ascending aorta and superior vena cava. After ventricular fibrillation, a left ventricular vent was placed through the right superior pulmonary vein, an aortic cross-clamp was applied when systemic temperature reached 20°C, and single-dose blood cardioplegia was administered. The right pulmonary artery was opened between the aorta and superior vena cava, with the incision extending into the proximal interlobar trunk. Loose thrombus was removed, and a thromboendarterectomy plane was established between medial and adventitial vessel layers. Under a brief period of circulatory arrest (ranging from 10 to 39 minutes), the thromboendarterectomy plane was developed distally into each segmental and subsegmental arterial branch of the right lung with removal of a pulmonary arterial tree "cast." After repair of the right pulmonary arteriotomy, during an interval of systemic reperfusion at 20°C, an intrapericardial left pulmonary arteriotomy was performed. During an additional period of hypothermic circulatory arrest, thromboendarterectomy was performed on the left. While patients were rewarming, coronary artery bypass grafting, mitral or tricuspid valve repair, aortic valve replacement, or foremen ovale closure was performed. Proximal coronary artery vein graft anastomoses were performed after removal of the aortic cross-clamp.

Statistical methods
Data were presented as mean ± standard deviation or median for continuous variables and as number (percentage) for categorical variables. Patient characteristics expressed as continuous variables and changes in perioperative hemodynamic parameters were compared between the PTE and the PTE-cardiac operation patient groups using independent Student’s t tests. A Pearson ² test was used to compare categorical variables. A p value less than 0.05 was considered to be statistically significant for each test, and no adjustment for multiple testing was used.

Times for cardiopulmonary bypass, cross-clamp, and circulatory arrest were compared between the PTE and the PTE-cardiac operation patient groups using Wilcoxon rank sum tests. The number (percentage) of subjects in each study group having a specified perioperative complication is descriptively reported.

	Results

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All 1,100 patients who underwent pulmonary thromboendarterectomy with or without foramen ovale closure and the 90 patients who underwent combined operation (CABG, CABG/foramen ovale closure, MV repair, AVR, or TV repair) underwent bilateral pulmonary thromboendarterectomy. Characteristics of patients at the time of operation are detailed in Table 1. The mean age for patients undergoing pulmonary thromboendarterectomy with or without foramen ovale closure was 50.4 years (range 24 to 82 years), while the mean age for patients undergoing combined operations was 68.1 years (range 48 to 82 years). The two patient groups were otherwise similar with respect to preoperative pulmonary artery pressures, pulmonary vascular resistance, and tricuspid regurgitant velocity. Patients undergoing combined operations had significantly lower preoperative cardiac output and relatively higher percentage of NYHA class IV symptoms compared with patients who underwent pulmonary thromboendarterectomy alone or in conjunction with foramen ovale closure. A proportion of pulmonary thromboendarterectomy patients had a previous history of deep venous thrombosis (40.5%) or pulmonary embolism (34.0%), while combined operation patients had a 43.7% history of deep venous thrombosis and 50.7% incidence of preoperative pulmonary embolism.

View larger version (40K): [in this window] [in a new window]   Fig 1. Comparison of cardiopulmonary bypass, cross-clamp, and circulatory arrest time in patients undergoing pulmonary endarterectomy and combined pulmonary endarterectomy-cardiac operations. (Open bar = pulmonary thromboendarterectomy; Solid bar = combined operation.)

	Comment

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Pulmonary hypertension secondary to chronic thromboembolic disease is a poor prognostic factor for long-term survival [9, 10]. Previous operative strategies for this form of pulmonary hypertension with or without resultant right heart failure have been limited to lung or heart-lung transplantation. In the last 12 years, our group has performed over 1,300 pulmonary thromboendarterectomies with an overall perioperative mortality of 5.3% and a 5-year survival of greater than 75%. In comparison, from 1990 to 1999, the UNOS Scientific Registry reported a 78% 1-month survival and 42% 5-year survival for single- and double-lung transplantation for pulmonary hypertension, and 67% 1-month survival and 36% 5-year survival for heart-lung transplantation for pulmonary hypertension. These results suggest that pulmonary thromboendarterectomy is the treatment of choice for chronic thromboembolic disease in the pulmonary arterial tree.

As pulmonary hypertension caused by chronic embolism and pulmonary thrombus has become better recognized due to more timely diagnosis, we have seen an increase in the number of older patients with this disease who present with concomitant coronary or valvular dysfunction. Since 1989, it has been our policy to screen all patients referred for pulmonary thromboendarterectomy older than 50 years with coronary angiography. Although transthoracic echocardiography is a routine part of our preoperative evaluation of right heart function and tricuspid regurgitation before pulmonary thromboendarterectomy, we use this study to also evaluate mitral and aortic valve function. With these methods, a subset of patients with both thromboembolic pulmonary hypertension and coronary or valvular disease have been identified. Interestingly, only one-third of these patients gave a history reflecting coronary or valvular disease.

Pulmonary hypertension from longstanding cardiac or pulmonary dysfunction has been identified as a multivariate risk factor for early morbidity and late mortality in cardiac surgical patients [11]. The degree of "fixed" pulmonary hypertension or pulmonary vascular resistance not attenuated by nitric oxide challenge as well as right ventricular dysfunction have served as determinants favoring heart or heart-lung transplantation in lieu of traditional coronary bypass and valve replacement operations [12]. Although previous studies suggest a link between elevated pulmonary vascular resistance and poor surgical outcome, they do not stratify patients with surgically accessible thromboembolic disease in the pulmonary vascular tree from other etiologies causing pulmonary hypertension.

We demonstrate in a small cohort of patients that cardiac operations such as coronary artery bypass grafting or replacement/repair of aortic, tricuspid, or mitral valves can be done safely in conjunction with pulmonary thromboendarterectomy. These combined operations result in perioperative mortality that are similar to that seen in patients undergoing pulmonary thromboendarterectomy alone or in conjunction with foramen ovale closure. It remains to be determined, however, whether patients undergoing coronary artery bypass or valve operations at the time of pulmonary thromboendarterectomy have long-term survival influenced by cardiac, pulmonary, or other factors. It is our impression that in patients undergoing pulmonary thromboendarterectomy that long-term mortality is not influenced by recurrent pulmonary hypertension unless: (1) new untreated pulmonary emboli occur, or (2) the pulmonary thromboendarterectomy was initially unsuccessful due to lack of thromboembolic material in the proximal pulmonary arterial tree [13, 14].

In this retrospective study, we did find that patients who underwent pulmonary thromboendarterectomy in conjunction with other major cardiac operations were on average more debilitated before surgery, had significantly longer hospital stays, and manifested more postoperative complications. This may reflect in part the older nature of the patient population undergoing combined operations, the severity of preoperative ventricular function of combined operation patients, and the extremely small number of patients undergoing pulmonary thromboendarterectomy and valve repair/replacement in this study. For both combined operation patients and isolated pulmonary thromboendarterectomy patients, gastrointestinal complications and pneumonia were the factors most associated with perioperative death. Although we report an incidence of postoperative delirium to be between 5% and 6% for both groups, over the last 10 years, this has largely improved to 2.5% of all pulmonary thromboendarterectomy patients due to shorter circulatory arrest periods, shorter-acting anesthetics, and early extubation practices at our institution.

Several operative points deserve mention in this study. First, the choice of operation should be individualized to the needs of each patient. Second, although tricuspid valve regurgitation is invariable in pulmonary hypertensive patients and is often severe due to annular dilatation, tricuspid valve repair is not routinely performed. We reserved tricuspid valve repair only for patients with a structural abnormality of tricuspid valve leaflets or chordae (ie, endocarditis with chordal rupture). Reduction of right ventricular size occurs within a few days after pulmonary thromboendarterectomy, with return of tricuspid competence in most patients. Third, foramen ovale closure with a running polypropylene suture is routinely performed in both isolated pulmonary thromboendarterectomy and combined operation patients who demonstrate echocardiographic evidence of right to left atrial shunting. This interatrial connection, resulting from right-sided pressure overload from long-standing pulmonary hypertension, was not a risk factor for surgical outcome in either group. Fourth, other cardiac procedures such as coronary artery or mitral or aortic valve surgery are conveniently performed during the systemic rewarming period.

This study underscores the need for screening older patients referred for pulmonary thromboendarterectomy for concomitant cardiac disease, and confirms that patients with thromboembolic pulmonary hypertension and coexisting cardiac disease may undergo combined pulmonary thromboendarterectomy and coronary bypass/valve operations with a successful outcome.

	Discussion

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DR W. RANDOLPH CHITWOOD, JR (Greenville, NC): I certainly appreciate the privilege of discussing this paper. I rise to congratulate Dr Thistlethwaite and her associates for a very nice presentation of important data from these very complex patients. I have read her excellent manuscript and will comment on it as well.

Clearly, the group from the University of California at San Diego has been preeminent in studying and surgically treating this lethal disease beginning around 1982. They have done thromboendarterectomies in over 1,300 patients with severe pulmonary hypertension from chronic, nonlysing pulmonary emboli since 1989. This was with an operative survival of 93%, which is excellent.

Today, Dr Thistlethwaite has shown positive results in 90 patients undergoing other cardiac procedures concomitant with thromboendarterectomy. Although these patients were older with poorer preoperative cardiac outputs, but with similar arrest and bypass times, both adjunctive coronary grafting and valvular surgery could be done with the same operative mortality as the primary surgical cohort.

Doctor Sabiston and our colleagues at Duke performed the first pulmonary embolectomy for chronic emboli in 1970. There, the surgical pathophysiology of this complex disease was first studied and defined. Our operative survival at that time was 86%.

These patients developed casts of nonlysed thrombolic material deep within the pulmonary vasculature. It becomes really attached to the vessel walls, obstructing both large and small vessels.

The hallmark of this disease is the lack of a single inciting embolus and the insidious vascular occlusion from multiple small and large pulmonary emboli, eventuating in chronic severe pulmonary hypertension and hypoxemia. As seen here, Reidel found early on that there was a direct correlation between severity of pulmonary hypertension and overall survival if untreated. Our studies at Duke showed that in selected patients, this operation affects significant decreases in pulmonary hypertension, as Dr Thistlethwaite has shown, with increased oxygenation and patient benefit and survival.

We also found a clear relationship between bronchial arterial inflow to obstructive pulmonary parenchyma and the benefit from endarterectomy. We used bronchial arteriography in each patient or angiography to define potential parenchymal perfusion distal to the occluding embolic cast. Confirmatory arterial back bleeding portended reestablishment of good pulmonary flow.

Doctor Thistlethwaite, firstly, did you observe any back bleeding in these cases? I noticed you closed the pulmonary artery after the circulatory arrest period. What are your predictors of a poor or a good operative outcome, and do you consider the presence of distal perfusion important to patient outcome?

Lastly, in the paper, you alluded to pulmonary hypertension in patients associated with coronary and valvular disease and combined with pulmonary hypertension from embolism. Preoperatively, do you study these patients to determine the level of reactive versus fixed pulmonary hypertension, and what are your exclusionary criteria for patients who are referred to you?

I consider your study a very important and informative one and would like to thank the Society for the opportunity to discuss this paper. Thank you.

DR THISTLETHWAITE: Thank you, Dr Chitwood. I would like to acknowledge you as one of the early leaders in the field and I have certainly enjoyed reading your papers.

In answers to your questions, number one, do we see back bleeding? The answer is yes. This is one of the major reasons why we use circulatory arrest in these patients because there is bronchial back bleeding that obscures the distal most part of the endarterectomy. We have almost universally seen that once one gets past the thromboembolic obstruction in the pulmonary arteries, that there is an open lumen, and so, yes, we do see back bleeding.

In answer to your second question, does distal perfusion affect outcome or back bleeding affect outcome, the answer is no. We have measured in 50 patients the amount of bronchial flow, both before and after surgery, when the aortic clamp was on. We do this by measuring blood coming back into our left atrial vent and also blood coming back into our main pulmonary arterial vent or when the pulmonary artery is open by measuring blood directly coming back into our cardiotomy suction. We have seen no correlation between bronchial artery blood flow and the degree of clot burden, nor the degree of pulmonary arterial obstruction, nor the degree of improvement in pulmonary vascular resistance in the postoperative period.

Question number three, with regards to fixed versus reactive pulmonary hypertension, all patients at our institution undergo pulmonary angiography as part of the screening process, and during this time they are given a nitric oxide challenge. They are also given a nitric oxide challenge during right heart catheterization. For the most part, our patients have all fixed pulmonary hypertension.

Your final question relating to exclusion criteria is a difficult one. I would say that there is no patient that we turn down based on the degree of right heart failure. We principally use the pulmonary angiogram as a measure of intravascular disease. There are a small subgroup of patients that are referred to us for the diagnosis of chronic thromboembolic disease that really have primary pulmonary hypertension, and these people have remarkably normal pulmonary angiograms. And so I would say that the principal exclusion that we use is a normal pulmonary angiogram in the setting of high pulmonary artery pressures.

Once again, thank you very much for your comments.

	References

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