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Ann Thorac Surg 1999;67:1350-1354
© 1999 The Society of Thoracic Surgeons

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Original Articles

Thoracic and cardiovascular interventions after orthotopic heart transplantation

^a Department of Thoracic and Cardiovascular Surgery, Heart Center North Rhine-Westphalia, University of Bochum, Bad Oeynhausen, Germany

Accepted for publication November 19, 1998.

Address reprint requests to Dr Koyanagi, Sakakibara Memorial Hospital, 2-5-4, Yoyogi, Shibuyaku, Tokyo, 151-0053, Japan

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. The long-term outcome of orthotopic heart transplantation is limited by the development of cardiac allograft vasculopathy, rejection, infection, and malignancy.

Methods. After heart transplantation, we treated patients with thoracic and cardiovascular diseases: preexisting coronary artery sclerosis in 2 patients, cardiac allograft vasculopathy in 19, valvular disease in 3, mycotic ascending aortic aneurysm in 2, superior vena cava stenosis in 2, and lung neoplasm in 10 patients.

Results. We successfully performed coronary artery bypass grafting for preexisting coronary artery sclerosis, valve replacement for valvular disease, and patch enlargement for superior vena cava stenosis. Percutaneous transluminal coronary angioplasty for cardiac allograft vasculopathy achieved excellent initial results, but the incidence of restenosis was high (67%). One patient who underwent coronary artery bypass grafting for cardiac allograft vasculopathy died immediately after operation. Graft replacement was performed for mycotic aortic aneurysm, but 1 patient required reoperation because of recurrent aneurysm. The long-term survival rate in patients undergoing surgical resection for lung neoplasm was poor (50%).

Conclusions. The need for thoracic and cardiovascular interventions in patients after heart transplantation was low (4.7%). Use of the appropriate procedures can improve the long-term survival after heart transplantation.

	Introduction

Top Abstract Introduction Material and methods Results Comment References

 
Orthotopic heart transplantation (HTx) has become an established treatment for end-stage heart disease. However, the shortage of donor organs is a major problem, and the long-term results are limited by the development of cardiac allograft vasculopathy (CAV), rejection, infection, and malignancy [1]. This article describes the clinical outcomes in patients with thoracic and cardiovascular interventions after HTx excluding retransplantation and mechanical circulatory support using ventricular assist device.

	Material and methods

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From March 1989 to December 1996, 801 HTx (673 men and 128 women) were carried out. The recipient age ranged from 3 days to 77 years (average, 50 years). The donor age ranged from 3 days to 65 years (average, 33 years). Graft ischemic time ranged from 88 to 332 minutes (average, 194 minutes). In the perioperative and at follow-up course, we performed surgical or percutaneous transluminal interventions for thoracic and cardiovascular diseases after HTx, consisting of transplant coronary artery disease in 21 patients (preexisting coronary artery sclerosis, 2; CAV, 19), transplant valvular disease in 3, mycotic aortic aneurysm in 2, stenosis of superior vena cava in 2, and lung neoplasm in 10 patients.

Donor procurement was performed using Bretschneider’s histidine-tryptophane-ketoglutarate solution. Bench coronary angiography (CAG) was ex vivo CAG of the donor heart before implantation [2]. Bench CAG was applied to patients suspected to have one-vessel coronary artery disease by inspection and palpation at explantation (Fig 1). If more than two-vessel disease was suspected, we rejected it as a donor heart. Recipient operation was performed with an atrial anastomosis according to the Lower-Shumway technique. Bicaval anastomosis was achieved mainly in patients with complex cardiac anomaly as an alternative method. Immunosuppression was based on initial triple-drug therapy, and subsequent long-term double-drug therapy, consisting of cyclosporine A (6 mg/kg per day) and azathioprine (2 mg/kg per day). The target level of cyclosporine A was 200 to 250 µg/L in adults during the first year. Whenever possible, steroid maintenance (10 mg/day) was avoided. Antiplatelet agents, including aspirin (50 mg) and dipyridamole (300 mg), were administered prophylactically to attempt to prevent CAV after HTx. If coronary artery disease was suspected, a calcium channel blocker, diltiazem (90 mg), was administered. In adult patients endomyocardial biopsy was performed first after the 19th postoperative day and every 2 to 3 weeks for 3 months, then every month for 1 year with increasing intervals according to the histologic grading and the clinical status of the patient. As prophylactic antibiotic therapy, cephalosporin was given until the chest tubes were removed. Baseline CAG was performed in transplant recipients having a donor heart of more than 50 years of age or with previous cardiopulmonary resuscitation, or being administered OKT3 due to ongoing rejection within 1 month after HTx. In the remainder of the patients, CAG was performed routinely 1 year after HTx [3].

View larger version (100K): [in this window] [in a new window]   Fig 1. Bench coronary angiography shows a 75% stenosis of the left anterior descending artery.

	Results

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Cardiac allograft vasculopathy
Coronary angioplasty was performed in 18 patients (15 men and 3 women) with CAV after HTx. The recipient age ranged from 50 to 68 years (average, 59.2 ± 5.7 years). The donor age ranged from 23 to 61 years (average, 45.4 ± 10 years). The interval from HTx to the first coronary angioplasty ranged from 1 month to 5 years (average, 27 ± 18.8 months). Each patient had a single focal stenosis; 12 lesions were found in the LAD, 5 in the left circumflex artery, and one in the right coronary artery. In 11 patients, the lesion was dilated with a balloon and in one with a rotablator. Lesion success rate (defined as an improvement of luminal diameter stenosis to <50%) was 100% and there were no major complications. However, restenosis rate (defined as a return of the same lesion to >50% stenosis) was high, 67%. Repeat coronary angioplasty was performed twice in 8 patients and three times in one. Two patients with restenosis underwent a stent implantation. During the mean follow-up period of 25.4 ± 17.6 months after the last coronary angioplasty, there were three cases of restenosis, no cases of retransplantation, and five late deaths, including one cardiac death due to acute myocardial infarction.

One patient underwent both coronary angioplasty and CABG for CAV. The patient was a 46-year-old man who underwent HTx for idiopathic cardiomyopathy. The donor heart was from a 58-year-old man and was suspected to have one-vessel coronary artery disease at explantation. However, the patient had already been on the transplant waiting list for more than 10 months, and the hemodynamic status began to deteriorate necessitating infusion of cathecholamine. Bench CAG was not performed. HTx procedure was performed uneventfully. Postoperative CAG revealed a 25% stenosis of the LAD. In the postoperative course, the patient showed several episodes of minimal or moderate rejection. Repeat CAG 15 months after HTx revealed rapidly accelerated CAV, demonstrating triple-vessel disease with multiple lesions. Coronary angioplasty was attempted in the posterodescending artery and the left circumflex artery. As a result, reduction of stenosis was obtained. However, subsequent CAG revealed immediate recurrence of stenosis and new lesions, involving the left main trunk (Fig 2). Although we proposed the necessity of retransplantation, he refused it on financial grounds, and we had no choice but to perform CABG. Saphenous veins were anastomosed to the right coronary artery, the second obtuse marginal branch, and proximal LAD. The distal LAD, which was diffusely diseased, was incised over a length of 3 cm. After endarterectomy, the left internal thoracic artery was anastomosed onto a vein patch that was sewn on the distal LAD. Because the patient was not able to be weaned off cardiopulmonary bypass, biventricular assist device was used. However, the patient died of multiple organ failure 3 days after operation.

View larger version (161K): [in this window] [in a new window]   Fig 2. Coronary angiography shows triple-vessel disease with multiple and diffuse lesions.

Mycotic aortic aneurysm
Two patients were diagnosed as having a mycotic ascending aortic aneurysm. Both patients were suspected to have mediastinal widening on chest roentgenogram. A false aneurysm was present at the site of previous aortic cannulation. Both patients underwent the transplant procedure uneventfully and were maintained by oral administration of low-dose steroid after HTx. One patient developed Pseudomonas pneumonia and hoarseness. At 8 months after HTx, the patient underwent debridement of the infected tissues and replacement of the ascending aorta with a collagen-sealed vascular graft (Hemashield) (Meadox Medicals Inc, Oakland, NJ). However, the patient required reoperation with a homograft because of recurrent false aneurysm at 2 months after operation. Nevertheless, the patient died of sudden bleeding from the airway due to bronchial fistula. In the other patient, Candida was detected in blood culture. At 18 months after HTx, the patient underwent replacement of the ascending aorta and extensive aortic arch with a Hemashield graft under circulatory hypothermic arrest with retrograde cerebral perfusion. The patient is alive.

Superior vena cava stenosis
In a 6-year-old child who had undergone Fontan operation for tricuspid atresia and an adult with previous CABG, a tiny right atrium was found and therefore, the HTx procedure was performed by means of bicaval anastomosis. They developed superior vena cava stenosis located at the site of the anastomosis. In the pediatric patient, there was a pressure gradient across the stenosis of 10 mm Hg. Patch enlargement of the superior vena cava was performed using a polytetrafluoroethylene patch under partial clamping without cardiopulmonary bypass. The pressure gradient decreased to 1 to 2 mm Hg after operation. In the adult patient, patch enlargement was successfully performed using a Dacron patch in the same manner.

Lung neoplasm
Lung neoplasms developed in 10 patients (9 men and 1 woman). The age at transplant ranged from 53 to 67 years (average, 58.7 ± 4.6 years). Seven patients had primary lung tumors and one patient had metastasis from a rectal carcinoma. Histologic types consisted of squamous cell carcinoma in 3 patients, adenocarcinoma in 5, adenosquamous carcinoma in 1, and bronchial carcinoid in 1 patient. They were treated surgically by lobectomy or wedge resection. The interval from HTx to surgical resection of the lung ranged from 8 to 59 months (average, 31.7 ± 15.5 months). During the mean postoperative follow-up period of 13.9 ± 11.2 months, 5 patients died.

	Comment

Top Abstract Introduction Material and methods Results Comment References

 
Between March 1989 and December 1996, we performed 801 orthotopic HTx. Early mortality (within 1 month after HTx) was 9.0% (n = 72) and late mortality (>1 month after HTx) was 19.5% (n = 156). The 1-year actuarial survival rate was 78% and 5-year survival was 70%. The main causes of late deaths were rejection, bacterial infection and sepsis, malignancy, aspergillosis, and cytomegaly. In suitable patients, transplant-related thoracic and cardiovascular diseases require surgical or percutaneous transluminal interventions perioperatively or at late follow-up.

Preexisting coronary artery sclerosis
Because of the shortage of suitable donor organs, we have extended the donor criteria [3]. Donors more than 50 years of age, donors receiving infusion of considerably high-dose catecholamines (dopamine >10 µg/kg/min, epinephrine >1 µg/kg/min), graft ischemic time more than 4 hours, or donor hearts with possible coronary artery sclerosis are accepted, taking the individual recipient’s prolonged waiting period and deteriorating hemodynamic status into consideration. Concurrent CABG at the same time as HTx is applied to patients with one-vessel coronary artery disease. We performed successful single CABG using a saphenous vein graft.

On the other hand, the internal thoracic artery may be a preferable conduit in expectation of long-term graft patency provided that the graft ischemic time is not prolonged. Postoperative CAG demonstrated a patent bypass graft in our 2 patients; nonetheless, accelerated stenosis developed in 1 patient in association with a new lesion. It seems that donor hearts with existing coronary artery disease should be used only for patients who are at very high risk of dying unless they receive HTx [4].

Cardiac allograft vasculopathy
The incidence of CAV as determined by angiographic and autopsy studies is between 1% and 18% at 1 year, and 40% and 50% at 5 years [5]. Cardiac allograft vasculopathy is assumed to be the major manifestation of chronic rejection, probably caused by immune-mediated endothelial injury of the graft. In addition, advanced donor age, female sex, pretransplant idiopathic cardiomyopathy, prolonged graft ischemic time, HLA mismatch, cytomegalovirus infection, hypercholesterolemia, hypertension, diabetes mellitus, smoking, and long-term corticosteroid administration are considered to contribute to the development of CAV [6]. The angiographic characteristics of CAV are a mixture of typical atherosclerotic lesions and unusual diffuse, concentric, and longitudinal narrowings prominent in middle-to-distal coronary vessels, with distal vessel obliteration and lack of collateral vessel formation [7].

Invasive therapeutic options for CAV include CABG, coronary angioplasty, and ultimately retransplantation. Coronary revascularization, whether by CABG or by coronary angioplasty, is generally not applicable to most patients with CAV because the disease process is diffuse, involving the distal vessels, and because it is frequently rapidly progressive [8]. A multicenter study demonstrated that balloon angioplasty of epicardial lesions in CAV had a lesion success rate of 94% (153 of 162 patients), which was comparable to that of routine angioplasty of atherosclerotic lesions. Restenosis was present in 42 of 76 lesions (55%) 8 ± 5 months (range, 2 to 19 months) after angioplasty [5]. We performed coronary angioplasty with excellent initial results, but the incidence of restenosis was relatively high (67%). Repeat coronary angioplasty were needed in 9 of 18 patients (50%). Because CAV is frequently progressive, subsequent multiple procedures may be required; nevertheless, coronary angioplasty appears to be the method of first choice to treat focal stenoses of CAV. Retransplantation is the only definitive therapy for CAV, but the survival rate is inferior compared with that for the initial HTx, and the incidence of recurrent CAV in the second graft is high [9].

We have attempted to prevent the development of CAV by means of prophylactic use of antiplatelet agents and calcium channel blockers, lipid-lowering medications, and control of hypertension [10]. Moreover, we have accomplished steroid-free long-term maintenance immunosuppression. Although the role of steroids in the development of CAV is uncertain, steroid-free maintenance may enable more effective control of steroid-related complications, such as hypertension, hyperlipidemia, diabetes mellitus, and obesity [11].

Transplant valvular disease
Tricuspid regurgitation is frequently found by echocardiography after HTx. The incidence of TR may be related to elevated pulmonary artery pressure and pulmonary vascular resistance, undersizing of the donor heart and distortion of the natural geometry, edema of valves and papillary muscles, right ventricular dysfunction and enlargement, the transplant technique used for atrial anastomosis, infective endocarditis, and endomyocardial biopsy [12]. Tucker and colleagues [13] reported flail tricuspid leaflet as a common complication of endomyocardial biopsy, occurring in 11.6% of patients who had undergone HTx. The mechanism of injury to a flail tricuspid leaflet most likely is inadvertent tearing of the individual chorda by the jaw of an endomyocardial biotome. We performed tricuspid valve replacement using the St. Jude Medical mechanical valve in 2 patients with TR related to endomyocardial biopsy, despite allowing no further endomyocardial biopsies and necessitating anticoagulant therapy [14]. Some investigators advocate tricuspid valve replacement using a bioprosthesis or valve repair. However, we believe that it is contraindicated to perform endomyocardial biopsy or right heart catheterization even through the bioprosthesis. However, Votapka and colleagues [15] reported that endomyocardial biopsy was able to be easily performed through the Hancock porcine valve and Stahl and associates [16] reported successful tricuspid valve repair by means of reattachment of the leaflet with a polytetrafluoroethylene suture and the use of a Carpentier-Edwards annuloplasty ring.

We performed mitral valve replacement in 1 patient because of increasing mitral regurgitation attributable to the development of annular dilatation. Mitral regurgitation may be related to atrial enlargement, leading to impaired functional integrity of the valvular apparatus. Owing to the continuity between the atrial endocardium and the posterior mitral leaflet, any displacement of the posterior atrial wall will exert tension on the posterior leaflet and therefore, may prevent complete closure of the valve.

Mycotic aortic aneurysm
Mycotic ascending aortic aneurysm is a rare yet life-threatening complication in immunosuppressed patients after HTx [17]. Mycotic aortic aneurysms occur at locations of diminished resistance of the aortic wall, such as aortic suture lines or cannulation sites, after microbial seeding. Microbial seeding can result from an untreated bacteremia in the donor, contamination during the organ harvesting procedure, or an inadequately treated infection in the recipient. The most common organisms are Staphylococcus aureus, Pseudomonas aeruginosa and other gram-negative bacilli, and Candida species. We performed prosthetic graft replacement in 2 patients with mycotic ascending aortic aneurysm. One patient required reoperation using a homograft because of recurrent false aneurysm. Complete removal of infected tissue is necessary to achieve satisfactory control of the infection [18]. The use of a cryopreserved aortic homograft appears to be favorable and promising as a material more resistant to infection. In patients with mediastinitis or incomplete debridement, transposition of an omental flap may be useful in spite of the potential for abdominal contamination. Postoperative antibiotic therapy for 4 to 6 weeks is recommended.

Superior vena cava stenosis
Bicaval anastomosis is recommended as an alternative technique of HTx. This technique consists of total excision of the recipient’s atria, with donor heart implantation performed using bicaval end-to-end anastomoses as well as pulmonary venous anastomoses [19]. The functional advantages of bicaval anastomosis, including better atrial transport, preservation of competent tricuspid and mitral valves, lower incidence of sinus arrhythmias, and less suture line thrombus formation, perhaps due to preservation of the geometric configuration, anatomic size, and physiologic function of the atria, can improve long-term hemodynamic results in patients after HTx. However, we have adopted the conventional technique of atrial anastomosis according to the Lower-Shumway technique, because the presence of Doppler-detected TR after HTx has been well tolerated clinically and the bicaval anastomosis may be associated with the possibility of SVC stenosis. Blanche and colleagues [19] reported that SVC stenosis developed postoperatively in 1 patient. Bicaval anastomosis may be technically more demanding in terms of suture line tension in patients with a major size discrepancy between donor and recipient, increasing the risk of caval narrowing. We successfully performed patch enlargement with partial clamping under stand-by cardiopulmonary bypass in 2 patients with SVC stenosis.

Lung neoplasm
The reported incidence of de novo malignant tumors in recipients after HTx varies from 1% to 16% (mean, 4%), an incidence approximately 100 times greater than that in the matched general population [20]. The most common neoplasms in cyclosporin-treated patients are cutaneous malignant tumors, non-Hodgkin’s lymphomas, carcinoma of the lung, and Kaposi’s sarcoma. Stronger immunosuppression may lead to greater impairment of surveillance mechanisms for neoplastic mutant cells. Other mechanisms may include increased viral oncogenesis and greater chronic antigenic stimulation by the donor heart with more aggressive immunosuppression. We surgically treated 10 patients with lung neoplasms, but the long-term survival rate was poor. Surgical treatment for patients after HTx with lung neoplasm is only palliative.

In conclusion, the need for thoracic and cardiovascular interventions in patients after HTx was low (4.7%). Using the appropriate procedures the long-term survival can be improved.

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Nils Reiss Nikolas Mirow Reiner Körfer Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Koyanagi, T. Articles by Körfer, R. Search for Related Content PubMed PubMed Citation Articles by Koyanagi, T. Articles by Körfer, R.