(Radiographics. 1999;19:321-341.)
© RSNA, 1999
Imaging of Cardiac Transplantation Complications
Barbara L. Knisely, MD1,
Lynn A. Mastey, MD1,
Jannette Collins, MD, MEd1 and
Janet E. Kuhlman, MD1
1 Department of Radiology (E3/311 CSC), University of Wisconsin Hospital and Clinics, 600 Highland Ave, Madison, WI 53792-3252.
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Abstract
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Common complications of cardiac transplantation include infection, rejection, accelerated coronary artery atherosclerosis, and lymphoproliferative disease. The authors reviewed radiographic and computed tomographic (CT) features of cardiac transplantation and its complications in a series of 232 patients (with 89 complications and 49 deaths). Normal postoperative findings in the first few weeks after surgery included enlarged cardiac silhouette, pneumomediastinum, pneumothorax, pneumopericardium, subcutaneous emphysema, and mediastinal widening. Infection was the most common complication, with pneumonia being the leading infectious condition (28 cases, with Aspergillus [n = 11] and cytomegalovirus [n = 10] being the most common pathogens) and the cause of death in seven cases. Although many cases of pulmonary infections occur in the first 3–4 months after surgery, in this series several cases developed up to 3 years afterward. Radiographic signs of acute rejection were nonspecific in the eight patients affected who died, and endomyocardial biopsy was used to confirm the suspected diagnosis. Accelerated atherosclerosis occurred in 13 patients between 10 months and 6.5 years after transplantation and led to death in eight. Lymphoproliferative disorders, which range from benign lymphoid hyperplasia to malignant lymphoma and which are the third leading cause of death beyond the immediate perioperative period in heart transplant recipients, developed in four patients who later died. Other complications related to endomyocardial biopsy and cardiothoracic surgery (ie, pneumothorax, hemothorax, pneumomediastinum, mediastinitis, aortic dissection, aortic pseudoaneurysm, and pulmonary embolism) occurred in 31 cases and were diagnosed with radiography and CT.
Index Terms: Heart, transplantation, 51.458, 51.459 • Surgery, complications, 51.458, 51.459
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INTRODUCTION
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Since the first successful cardiac transplantation performed in 1967, over 34,000 such operations have been recorded by the Registry of the International Society for Heart and Lung Transplantation (1). Cardiac transplantation is the currently accepted treatment for end-stage cardiomyopathy and coronary artery disease and has 1- and 5-year survival rates of 79% and 63%, respectively (1). Improvements in immunosuppression techniques and the widespread use of endomyocardial biopsy to diagnose rejection account for most of the improvement in early survival statistics (2). Infection and rejection remain significant causes of morbidity and death despite improvements in immunosuppression techniques (2), with the most common complications of cardiac transplantation being infection, rejection, accelerated coronary artery atherosclerosis, and posttransplantation lymphoproliferative disease (3–5).
In this article, we present the chest radiographic and computed tomographic (CT) appearances of common complications seen in cardiac transplant recipients. We review the postoperative anatomy of the transplanted heart and its normal radiologic appearance and discuss the complications directly related to cardiac transplantation, those related to endomyocardial biopsy, and those related to cardiothoracic surgery.
Our observations are based on a review of the clinical course and imaging studies of 232 patients who underwent orthotopic (n = 231) and heterotopic (n = 1) cardiac transplantation at our institution from November 1989 to November 1996. Among our group of transplant recipients, the mean patient age was 52 years (range, 13–71 years); 189 of the patients were men, and 43 were women. Causes of cardiomyopathy were ischemic (n = 117), idiopathic (n = 97), viral (n = 6), congenital (n = 4), valvular (n = 4), sarcoidosis (n = 1), arrhythmia (n = 1), restrictive (n = 1), and doxorubicin toxicity (n = 1). Forty-nine deaths occurred related to 89 complications. The deaths were related to severe acute rejection (n = 8), accelerated atherosclerosis (n = 8), sepsis (n = 3), multisystem organ failure (n = 3), bleeding (n = 3), malignancy (n = 3), disseminated Aspergillus infection (n = 2), failure to wean from cardiopulmonary bypass (n = 2), and nonspecific graft failure (n = 2). In 15 cases, cause of death was unknown.
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POSTOPERATIVE ANATOMY AND NORMAL POSTOPERATIVE APPEARANCE OF TRANSPLANTED HEARTS
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Orthotopic Cardiac Transplant
In orthotopic cardiac transplantation, the recipient's heart is removed through a median sternotomy, and a cuff of both native atria and severed ends of the ascending aorta and main pulmonary artery is retained (Fig 1). The donor heart is joined to the recipient's atria, aorta, and pulmonary artery. The donor superior vena cava stump is tied just above the right atrium, and the donor inferior vena cava is incorporated into the right atrial anastomosis.
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Figure 1a. Orthotopic cardiac transplantation. (a) Diagram shows intraoperative appearance of native and donor hearts before surgical connection of the atria, pulmonary artery, and aorta. (b) Illustration shows the four anastomoses in the completed orthotopic cardiac transplantation. AO = aorta, LA = left atrium, LV = left ventricle, PA = pulmonary artery, RA = right atrium, RV = right ventricle, SVC = superior vena cava.
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Figure 1b. Orthotopic cardiac transplantation. (a) Diagram shows intraoperative appearance of native and donor hearts before surgical connection of the atria, pulmonary artery, and aorta. (b) Illustration shows the four anastomoses in the completed orthotopic cardiac transplantation. AO = aorta, LA = left atrium, LV = left ventricle, PA = pulmonary artery, RA = right atrium, RV = right ventricle, SVC = superior vena cava.
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At chest radiography, the normal postoperative appearance typically includes an enlarged cardiac silhouette because of the discrepancy in sizes between the transplanted heart and the native pericardium (Fig 2) (6). Pericardial effusions are occasionally seen as a result of placing a small donor heart into a larger pericardial sac or after immunotherapy with cyclosporine (7,8). The size of the cardiac silhouette decreases over several months. A double right atria contour, caused by overlap of donor and recipient right atria, may also be seen on postoperative chest radiographs (7). Pneumomediastinum, pneumothorax, pneumopericardium, and subcutaneous emphysema are frequently present immediately following median sternotomy and resolve over several days. Mediastinal widening is seen in all cases for 1–2 weeks after transplantation because of postoperative mediastinal bleeding secondary to the extensive resection (9). Mediastinal fluid collections and substernal pockets of air are normal findings in the first 20 days following sternotomy. Delayed mediastinal widening may be related to steroid-induced mediastinal fat deposition.
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Figure 2. Orthotopic cardiac transplantation in a 64-year-old woman with ischemic cardiomyopathy. AP recumbent chest radiograph obtained immediately after transplantation shows an enlarged cardiac silhouette, pulmonary edema, and bibasilar atelectasis. Bilateral thoracostomy tubes, endotracheal tube, esophageal temperature probe, left subclavian venous catheter, pulmonary artery catheter, and sternal wires are also seen.
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At CT, the normal postoperative appearance of the heart and great vessels may include a high, redundant main pulmonary artery (10) (Fig 3). A large space may exist between the recipient superior vena cava and donor ascending aorta and between the donor ascending aorta and main pulmonary artery. The size of the recipient ascending aorta may differ from that of the donor aorta. A radiosynthetic patch may encircle either the aortic or pulmonic anastomosis. The remnant donor superior vena cava may appear posterior to the donor ascending aorta and medial to the recipient superior vena cava (Fig 4). The anastomosis of the atria may cause an indentation or waist in the atria. The native inferior vena cava may be larger than the donor vessel.
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Figure 3a. Mediastinal lipomatosis in a 61-year-old man who underwent orthotopic cardiac transplantation for ischemic cardiomyopathy 3 years before. (a) AP upright chest radiograph shows a wide mediastinum, an appearance consistent with mediastinal adenopathy or mediastinal lipomatosis. (b) Nonenhanced chest CT scan shows a superior redundant main pulmonary artery (arrowhead), a large space (large arrow) between the recipient superior vena cava and donor ascending aorta, and aortic anastomosis suture lines (small arrows) and helps confirm that mediastinal lipomatosis accounts for the wide mediastinum. (c) CT scan obtained inferior to b shows pulmonic anastomosis suture lines (arrows).
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Figure 3b. Mediastinal lipomatosis in a 61-year-old man who underwent orthotopic cardiac transplantation for ischemic cardiomyopathy 3 years before. (a) AP upright chest radiograph shows a wide mediastinum, an appearance consistent with mediastinal adenopathy or mediastinal lipomatosis. (b) Nonenhanced chest CT scan shows a superior redundant main pulmonary artery (arrowhead), a large space (large arrow) between the recipient superior vena cava and donor ascending aorta, and aortic anastomosis suture lines (small arrows) and helps confirm that mediastinal lipomatosis accounts for the wide mediastinum. (c) CT scan obtained inferior to b shows pulmonic anastomosis suture lines (arrows).
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Figure 3c. Mediastinal lipomatosis in a 61-year-old man who underwent orthotopic cardiac transplantation for ischemic cardiomyopathy 3 years before. (a) AP upright chest radiograph shows a wide mediastinum, an appearance consistent with mediastinal adenopathy or mediastinal lipomatosis. (b) Nonenhanced chest CT scan shows a superior redundant main pulmonary artery (arrowhead), a large space (large arrow) between the recipient superior vena cava and donor ascending aorta, and aortic anastomosis suture lines (small arrows) and helps confirm that mediastinal lipomatosis accounts for the wide mediastinum. (c) CT scan obtained inferior to b shows pulmonic anastomosis suture lines (arrows).
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Figure 4a. Anastomotic connections in a 45-year-old man who underwent orthotopic cardiac transplantation for idiopathic cardiomyopathy. (a, b) Sequential contrast material–enhanced CT scans reveal change in caliber from the recipient to donor ascending aorta (arrow). (c) CT scan obtained inferior to b shows remnant donor superior vena cava (large arrow) posterior to the donor ascending aorta (arrowhead) and medial to the recipient superior vena cava (small arrow).
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Figure 4b. Anastomotic connections in a 45-year-old man who underwent orthotopic cardiac transplantation for idiopathic cardiomyopathy. (a, b) Sequential contrast material–enhanced CT scans reveal change in caliber from the recipient to donor ascending aorta (arrow). (c) CT scan obtained inferior to b shows remnant donor superior vena cava (large arrow) posterior to the donor ascending aorta (arrowhead) and medial to the recipient superior vena cava (small arrow).
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Figure 4c. Anastomotic connections in a 45-year-old man who underwent orthotopic cardiac transplantation for idiopathic cardiomyopathy. (a, b) Sequential contrast material–enhanced CT scans reveal change in caliber from the recipient to donor ascending aorta (arrow). (c) CT scan obtained inferior to b shows remnant donor superior vena cava (large arrow) posterior to the donor ascending aorta (arrowhead) and medial to the recipient superior vena cava (small arrow).
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Heterotopic Cardiac Transplant
Heterotopic cardiac transplantation is reserved for patients who have high pulmonary vascular resistance, who receive a small donor organ, or who have acute or potentially reversible myocardial dysfunction (11). In heterotopic cardiac transplantation, the donor heart is placed in the right thoracic cavity and connected to the recipient's heart in such a manner that the native right ventricle provides the majority of right-side cardiac output and the donor left ventricle provides the bulk of left-side cardiac output (Fig 5). Disadvantages of this procedure include angina, arrhythmias, and risk of thromboembolism from the recipient's native heart (12). Long-term therapy with anticoagulants is required to prevent potential systemic embolization.
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Figure 5. Heterotopic cardiac transplantation. Illustration shows the anastomoses and the relationship of the donor heart to the recipient heart. AO = aorta, LV = left ventricle, PA = pulmonary artery, RA = right atrium, RV = right ventricle, SVC = superior vena cava.
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At chest radiography, the heterotopic donor heart is located in the right hemithorax, lateral to patient's native heart (Fig 6). The patient may appear to have a markedly enlarged heart if the heterotopic nature of the transplanted organ is not known. Substantial atelectasis in the right lower lobe may occur from the position of the heterotopic heart (13).
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Figure 6. Heterotopic cardiac transplantation in a 55-year-old man with ischemic cardiomyopathy for whom orthotopic cardiac transplantation was precluded because of severe pulmonary hypertension. PA upright chest radiograph obtained 6 years after transplantation shows an enlarged cardiac silhouette, with the donor heart in the right hemothorax, lateral to the patient's native heart. Radiosynthetic patch encircles the aortic anastomosis (arrows).
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COMPLICATIONS DIRECTLY RELATED TO CARDIAC TRANSPLANTATION
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Infection
Infection accounts for about 40% of the deaths after cardiac transplantation (2). Infectious complications occur in 40%–80% of cardiac transplant recipients (14), with pneumonia being the leading infectious complication (24%–40% of cases) (15,16). In our patient group, infectious events accounted for 34 of 89 complications and included Aspergillus pneumonia (n = 11), cytomegalovirus (CMV) pneumonia (n = 10), bacterial pneumonia (n = 5), Pseudomonas pneumonia (n = 2), disseminated Aspergillus infection (n = 2), abdominal abscess (n = 2), Exophiala pneumonia (n = 1), and pulmonary abscess (n = 1). Three patients had pneumonia caused by multiple bacterial, viral, and fungal pathogens (CMV and Aspergillus and Pseudomonas organisms).
Most pulmonary infections occur within the first 3–4 months following heart transplantation, with most fatal infections developing during this period (15). About 20%–25% of infection-related deaths are caused by multiple pathogens (15). Empyema and mediastinitis, in addition to pneumonia, are often associated with an unfavorable outcome (17).
Reported frequency of and death from Aspergillus pneumonia in cardiac transplant recipients ranges from 11% to 16% (9,10) and 54% to 86% (2,18), respectively. In our group, 11 cases of Aspergillus pneumonia occurred between 11 days and 17 months after transplantation (mean, 6 months) (Fig 7), and this infection was related to the cause of death in six patients (Fig 8). Four patients died of pneumonia, and two developed disseminated Aspergillus infection and eventually died: In one patient, infection spread to the skin, kidney, and adrenal gland, and in the other patient, infection spread to the brain.
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Figure 7a. Figures 7, 8. (7) Pulmonary A fumigatus infection in a 40-year-old man who developed dyspnea 10 months after cardiac transplantation for idiopathic cardiomyopathy. (a) PA upright chest radiograph shows numerous ill-defined nodular opacities in the right lung. (b) CT scan reveals multiple, fuzzy nodules in the right lung, consistent with pulmonary Aspergillus infection. Diagnosis was confirmed with bronchoalveolar lavage, and the patient recovered after a course of amphotericin. (8) Aspergillus pneumonia in a 60-year-old man who developed productive cough and dyspnea 8 months after cardiac transplantation for idiopathic cardiomyopathy. (a) PA upright chest radiograph shows a cavitary mass (arrows) in the right lower lobe and diffuse interstitial lung disease. (b) Thin-section CT scan shows the cavitary mass with a ground-glass "halo" (arrows) representing hemorrhage, a finding consistent with invasive Aspergillus infection. Basilar honeycombing is consistent with idiopathic pulmonary fibrosis.
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Figure 7b. Figures 7, 8. (7) Pulmonary A fumigatus infection in a 40-year-old man who developed dyspnea 10 months after cardiac transplantation for idiopathic cardiomyopathy. (a) PA upright chest radiograph shows numerous ill-defined nodular opacities in the right lung. (b) CT scan reveals multiple, fuzzy nodules in the right lung, consistent with pulmonary Aspergillus infection. Diagnosis was confirmed with bronchoalveolar lavage, and the patient recovered after a course of amphotericin. (8) Aspergillus pneumonia in a 60-year-old man who developed productive cough and dyspnea 8 months after cardiac transplantation for idiopathic cardiomyopathy. (a) PA upright chest radiograph shows a cavitary mass (arrows) in the right lower lobe and diffuse interstitial lung disease. (b) Thin-section CT scan shows the cavitary mass with a ground-glass "halo" (arrows) representing hemorrhage, a finding consistent with invasive Aspergillus infection. Basilar honeycombing is consistent with idiopathic pulmonary fibrosis.
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Figure 8a. Figures 7, 8. (7) Pulmonary A fumigatus infection in a 40-year-old man who developed dyspnea 10 months after cardiac transplantation for idiopathic cardiomyopathy. (a) PA upright chest radiograph shows numerous ill-defined nodular opacities in the right lung. (b) CT scan reveals multiple, fuzzy nodules in the right lung, consistent with pulmonary Aspergillus infection. Diagnosis was confirmed with bronchoalveolar lavage, and the patient recovered after a course of amphotericin. (8) Aspergillus pneumonia in a 60-year-old man who developed productive cough and dyspnea 8 months after cardiac transplantation for idiopathic cardiomyopathy. (a) PA upright chest radiograph shows a cavitary mass (arrows) in the right lower lobe and diffuse interstitial lung disease. (b) Thin-section CT scan shows the cavitary mass with a ground-glass "halo" (arrows) representing hemorrhage, a finding consistent with invasive Aspergillus infection. Basilar honeycombing is consistent with idiopathic pulmonary fibrosis.
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Figure 8b. Figures 7, 8. (7) Pulmonary A fumigatus infection in a 40-year-old man who developed dyspnea 10 months after cardiac transplantation for idiopathic cardiomyopathy. (a) PA upright chest radiograph shows numerous ill-defined nodular opacities in the right lung. (b) CT scan reveals multiple, fuzzy nodules in the right lung, consistent with pulmonary Aspergillus infection. Diagnosis was confirmed with bronchoalveolar lavage, and the patient recovered after a course of amphotericin. (8) Aspergillus pneumonia in a 60-year-old man who developed productive cough and dyspnea 8 months after cardiac transplantation for idiopathic cardiomyopathy. (a) PA upright chest radiograph shows a cavitary mass (arrows) in the right lower lobe and diffuse interstitial lung disease. (b) Thin-section CT scan shows the cavitary mass with a ground-glass "halo" (arrows) representing hemorrhage, a finding consistent with invasive Aspergillus infection. Basilar honeycombing is consistent with idiopathic pulmonary fibrosis.
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Systemic Exophiala fungal disease developed in one patient related to a toe infection 3 months after transplantation (Fig 9). The patient was treated successfully with antifungal therapy.
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Figure 9. Fungal pneumonia in a 46-year-old woman who developed pleuritic right-sided chest pain 3 months after cardiac transplantation for ischemic cardiomyopathy. Thin-section CT scan shows multiple 1–3-mm subpleural nodules (small arrows) and a nodule in the medial right lower lobe (large arrow), compatible with systemic spread of a rare fungal (Exophiala) infection of her toe that responded to multidrug antifungal therapy.
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The frequency of CMV pneumonitis in cardiac transplant recipients ranges from 9% to 11%, with death occurring in 14% (10,14). Diffuse pulmonary air-space disease is the predominant radiographic finding, with focal air-space disease seen in up to one-third of patients (15,16) (Fig 10). Our 10 cases of CMV pneumonia occurred between 2 months to 3 years (mean, 10 months) after transplantation. Eight patients were treated effectively with ganciclovir and remain alive. Ganciclovir is an antiviral agent effective for both prophylaxis and treatment of CMV infections. One patient died of CMV sepsis, and one patient with CMV and Aspergillus pneumonia died of brain stem herniation secondary to multiple Aspergillus brain abscesses.
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Figure 10. CMV pneumonia in a 57-year-old woman who developed fever and shortness of breath 10 weeks after cardiac transplantation for restrictive cardiomyopathy. Contrast-enhanced CT scan reveals a consolidated right lower lobe with air bronchograms and a small right pleural effusion. Transbronchial biopsy specimens from the right lung showed large CMV intracytoplasmic inclusion bodies.
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Most bacterial pneumonias occur in the first 2–3 weeks after transplantation (14). The frequency of bacterial infections after cardiac transplantation in patients treated with cyclosporine has decreased. Aerobic gram-negative rods are the predominant bacterial organisms (14,15). Our five cases of bacterial pneumonia occurred between 1 day and 30 months (mean, 11.6 months) after transplantation. Four patients responded to antibiotic therapy (Fig 11). One patient developed gram-negative sepsis, two right pulmonary abscesses, and multisystem organ failure 3 months following transplantation and died (Fig 12).
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Figure 11. Haemophilus influenzae pneumonia in a 60-year-old man who presented with productive cough, fever, and chills 8 weeks after cardiac transplantation. Nonenhanced CT scan shows bilateral pleural effusions and left lower lobe consolidation. Sputum cultures were positive for H influenzae, and the patient responded to intravenous treatment with antibiotics.
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Figure 12. Pulmonary abscess in a 44-year-old man who developed increasing shortness of breath and fatigue after cardiac transplantation for familial cardiomyopathy. Nonenhanced CT scan shows a 3.5-cm mass in the right upper lobe with a central area of low attenuation consistent with necrosis and surrounding air-space disease. The patient developed gram-negative sepsis leading to multisystem organ failure and died 8 days later.
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Immunocompromised patients are susceptible to acute diverticulitis, which occurs in 0%–4% of cardiac transplant recipients (19). In our group, two patients developed bowel perforations and abdominal abscesses from diverticulitis and small bowel ischemia at 2 months and 2 weeks after transplantation, respectively. The patient with diverticulitis underwent total colectomy and partial small bowel resections for multiple perforations.
Acute Allograft Rejection
Acute rejection is defined histologically as lymphocytic infiltration of the myocardium with myocyte necrosis and usually occurs between 2 weeks and 3 months after transplantation (3). According to the Cardiac Transplant Research Database, rejection risk is highest in the first postoperative months and decreases dramatically within 6 months of transplantation (20). Death from acute rejection occurs in approximately 3% of patients at 18 months after transplantation (20).
Patients experiencing acute rejection present clinically with dyspnea, lethargy, weakness, hypotension, or heart failure. Cardiomegaly may be demonstrated on chest radiographs; however, this sign is neither specific nor sensitive for rejection (Fig 13).
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Figure 13a. Acute allograft rejection in a 62-year-old man who developed hypotension and congestive heart failure 10 weeks after cardiac transplantation for dilated cardiomyopathy. (a) AP upright chest radiograph shows an enlarged cardiac silhouette, pulmonary edema, and bilateral pleural effusions. The postoperative image also reveals sternal wires, endotracheal tube, nasogastric tube, right subclavian venous catheter, and pulmonary artery catheter in the distal right lower lobe interlobar pulmonary artery. (b) High-power photomicrograph (original magnification, x400; hematoxylin-eosin stain) shows diffuse lymphocytic infiltration of the myocardium with patchy myocyte necrosis.
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Figure 13b. Acute allograft rejection in a 62-year-old man who developed hypotension and congestive heart failure 10 weeks after cardiac transplantation for dilated cardiomyopathy. (a) AP upright chest radiograph shows an enlarged cardiac silhouette, pulmonary edema, and bilateral pleural effusions. The postoperative image also reveals sternal wires, endotracheal tube, nasogastric tube, right subclavian venous catheter, and pulmonary artery catheter in the distal right lower lobe interlobar pulmonary artery. (b) High-power photomicrograph (original magnification, x400; hematoxylin-eosin stain) shows diffuse lymphocytic infiltration of the myocardium with patchy myocyte necrosis.
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The diagnosis of rejection is made with endomyocardial biopsy (21). However, because of the invasiveness of this technique, nuclear cardiography is being investigated for its potential in the detection of allograft rejection. In one study, those cases with increased cardiac uptake on gallium-67 scintigraphic images also had histologic evidence (from endomyocardial biopsy) of moderate or severe rejection (22). Nuclear cardiography, as an alternative method for rejection surveillance, may reduce costs and morbidity for select patients (22).
In our group, eight patients developed severe acute rejection and were treated with high doses of steroids and with monoclonal antibody OKT3, but all eight died. OKT3 is an anti–T-lymphocyte antibody used in the treatment of acute cardiac allograft rejection. These rejection episodes developed from 1 day to 9 months (mean, 2.6 months) following transplantation.
Accelerated Graft Atherosclerosis
Accelerated graft atherosclerosis is defined histologically as concentric intimal proliferation composed of modified smooth muscle cells, macrophages, and lymphocytes (23). Progressive intimal thickening diffusely obliterates coronary artery lumens, causing ischemic allograft failure. Angiographic evidence of accelerated coronary artery atherosclerosis is seen in up to 50% of transplant recipients by 5 years after transplantation (24). Approximately 40% of deaths and cases of retransplantation are related to accelerated graft atherosclerosis (24). In our group, accelerated atherosclerosis occurred in 13 of 232 patients, between 10 months and 6.5 years after transplantation (mean, 2.25 years).
Coronary angiography and intracoronary ultrasonography are methods currently used to detect accelerated coronary artery atherosclerosis (25). Recent studies indicate that coronary artery calcification is a marker of active atherosclerotic plaque development (26). Early work with noninvasive ultrafast CT showed good correlation between coronary artery calcification seen on CT scans and angiograms, and the quantity of calcifications on CT scans was a good predictor of subsequent cardiac events (27).
Malignancy
The prevalence of malignancy after transplantation is estimated to be 4% or 100 times greater than that for the general population (28). The most frequently observed tumors are squamous cell carcinoma of the skin, adenocarcinomas of the lung and gastrointestinal tract, Kaposi sarcoma, acute leukemia, and lymphoma (29). The increased prevalence of malignancy is thought to be related to the use of cytotoxic agents for immunosuppression.
Posttransplantation lymphoproliferative disorder occurs in 2%–6% of cardiac transplant recipients (30). Most lymphoproliferative disorders are of B-cell origin and are associated with Epstein-Barr virus infection (31). The third leading cause of death beyond the immediate perioperative period in heart transplant recipients is lymphoproliferative disorders, which range from benign lymphoid hyperplasia to malignant lymphoma (5). Pulmonary manifestations of posttransplantation lymphoproliferative disorder include a solitary mass, multiple noncavitating nodules, and mediastinal or hilar adenopathy (32,33).
In our group, two patients developed posttransplantation lymphoproliferative disorder at 8 and 9 months after the surgery (Fig 14). Reduction of immunosuppression was the treatment for both patients; however, both died 2 and 10 months later of an unknown cause and an arrhythmia, respectively. Two patients developed lymphoma at 11 and 12 months (Fig 15). Both died shortly after diagnosis, related to gram-negative sepsis and rectus sheath hemorrhage, respectively. One patient developed biopsy-proved Kaposi sarcoma of the lower extremity, which was diagnosed shortly before the patient died of sepsis. One patient developed squamous cell carcinoma at her tracheostomy site 4 years after transplantation; the cancer was treated with surgical resection. One patient died as a result of metastatic adenocarcinoma of the lung 3 months after cardiac transplantation (Fig 16). A recent report showed a high prevalence of bronchogenic carcinoma in cardiac transplant recipients (34). An earlier report described sporadic cases of carcinoma of the lung, breast, and colon in these patients (35).
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Figure 14a. Lymphoproliferative disorder in a 65-year-old man who presented without symptoms after cardiac transplantation for ischemic cardiomyopathy. (a) PA upright chest radiograph reveals a lingular mass and small left pleural nodular opacity (arrow). (b) Nonenhanced CT scan reveals a left pleural-based nodule. (The patient's allergy to contrast material prevented its use.) (c) CT scan obtained inferior to b reveals a mass abutting the left atrium (arrow). (d) T1-weighted magnetic resonance image shows frank invasion of the mass into the left atrium. Findings from open lung endomyocardial biopsy were consistent with lymphoproliferative disorder. The patient died 7 months later of an arrhythmia.
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Figure 14b. Lymphoproliferative disorder in a 65-year-old man who presented without symptoms after cardiac transplantation for ischemic cardiomyopathy. (a) PA upright chest radiograph reveals a lingular mass and small left pleural nodular opacity (arrow). (b) Nonenhanced CT scan reveals a left pleural-based nodule. (The patient's allergy to contrast material prevented its use.) (c) CT scan obtained inferior to b reveals a mass abutting the left atrium (arrow). (d) T1-weighted magnetic resonance image shows frank invasion of the mass into the left atrium. Findings from open lung endomyocardial biopsy were consistent with lymphoproliferative disorder. The patient died 7 months later of an arrhythmia.
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Figure 14c. Lymphoproliferative disorder in a 65-year-old man who presented without symptoms after cardiac transplantation for ischemic cardiomyopathy. (a) PA upright chest radiograph reveals a lingular mass and small left pleural nodular opacity (arrow). (b) Nonenhanced CT scan reveals a left pleural-based nodule. (The patient's allergy to contrast material prevented its use.) (c) CT scan obtained inferior to b reveals a mass abutting the left atrium (arrow). (d) T1-weighted magnetic resonance image shows frank invasion of the mass into the left atrium. Findings from open lung endomyocardial biopsy were consistent with lymphoproliferative disorder. The patient died 7 months later of an arrhythmia.
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Figure 14d. Lymphoproliferative disorder in a 65-year-old man who presented without symptoms after cardiac transplantation for ischemic cardiomyopathy. (a) PA upright chest radiograph reveals a lingular mass and small left pleural nodular opacity (arrow). (b) Nonenhanced CT scan reveals a left pleural-based nodule. (The patient's allergy to contrast material prevented its use.) (c) CT scan obtained inferior to b reveals a mass abutting the left atrium (arrow). (d) T1-weighted magnetic resonance image shows frank invasion of the mass into the left atrium. Findings from open lung endomyocardial biopsy were consistent with lymphoproliferative disorder. The patient died 7 months later of an arrhythmia.
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Figure 15a. Lymphoma in a 64-year-old man who developed shortness of breath 13 months after cardiac transplantation. (a) PA chest radiograph shows a right paratracheal mass (arrow) and right pleural effusion. (b) Contrast-enhanced CT scan shows the large anterior mediastinal mass lateral to and abutting the aortic arch, causing extrinsic compression on the superior vena cava and left brachiocephalic vein. Analysis of right thoracentesis fluid revealed findings consistent with monoclonal large cell lymphoma. The patient developed sepsis and died 3 weeks later of a major retroperitoneal hemorrhage while receiving heparin for pulmonary embolus.
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Figure 15b. Lymphoma in a 64-year-old man who developed shortness of breath 13 months after cardiac transplantation. (a) PA chest radiograph shows a right paratracheal mass (arrow) and right pleural effusion. (b) Contrast-enhanced CT scan shows the large anterior mediastinal mass lateral to and abutting the aortic arch, causing extrinsic compression on the superior vena cava and left brachiocephalic vein. Analysis of right thoracentesis fluid revealed findings consistent with monoclonal large cell lymphoma. The patient developed sepsis and died 3 weeks later of a major retroperitoneal hemorrhage while receiving heparin for pulmonary embolus.
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Figure 16a. Bronchogenic carcinoma in a 65-year-old man who developed shortness of breath 3 months after cardiac transplantation for ischemic cardiomyopathy. (a) PA upright chest radiograph shows recurrent right pleural effusion, a left upper lobe mass (arrow), and peripheral interstitial disease. (b) CT scan shows air bronchograms within the left upper lobe mass, as well as low-attenuation areas throughout the lung parenchyma consistent with emphysema and superimposed interstitial disease consistent with amiodarone toxicity. Findings from transbronchial biopsy were consistent with bronchogenic carcinoma. The patient died of cardiopulmonary arrest related to metastatic bronchogenic carcinoma 1 week later.
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Figure 16b. Bronchogenic carcinoma in a 65-year-old man who developed shortness of breath 3 months after cardiac transplantation for ischemic cardiomyopathy. (a) PA upright chest radiograph shows recurrent right pleural effusion, a left upper lobe mass (arrow), and peripheral interstitial disease. (b) CT scan shows air bronchograms within the left upper lobe mass, as well as low-attenuation areas throughout the lung parenchyma consistent with emphysema and superimposed interstitial disease consistent with amiodarone toxicity. Findings from transbronchial biopsy were consistent with bronchogenic carcinoma. The patient died of cardiopulmonary arrest related to metastatic bronchogenic carcinoma 1 week later.
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COMPLICATIONS OF ENDOMYOCARDIAL BIOPSY
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Endomyocardial biopsy is currently the accepted method for diagnosing cardiac allograft rejection. The technique of transvenous right ventricular endomyocardial biopsy was described in 1962 (36). Biopsy specimens are usually taken from the right ventricular septal wall. Complications of the procedure, which are related to obtaining venous access, include pneumothorax and hemothorax.
In our group, two patients developed pneumothorax (one in the left lung, one in the right) following endomyocardial biopsy that resolved with chest tube placement (Fig 17). Of the two patients who developed hemothorax (one in the left lung, one in the right), one suffered cardiovascular collapse and died; the second required no intervention (Fig 18).
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Figure 17. Pneumothorax following endomyocardial biopsy in a 57-year-old man who developed shortness of breath after the biopsy 6 months after cardiac transplantation. AP upright chest radiograph reveals a large right pneumothorax. The patient recovered following chest tube placement and returned home 6 days later.
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Figure 18. Hemothorax following endomyocardial biopsy in a 59-year-old man who developed mild shortness of breath after the biopsy. Nonenhanced CT scan shows a high-attenuation left pleural effusion consistent with hemothorax (arrow). The patient recovered without intervention.
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COMPLICATIONS RELATED TO CARDIOTHORACIC SURGERY
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Chest Wall and Mediastinal Complications
Cardiac transplantation involves a sternal incision, which can lead to the development of poststernotomy complications. Complication rates after sternotomy are 2%–5%, and death occurs in 27% of cases from mediastinal infections and in 50% of cases from diffuse mediastinitis (37,38).
At radiography, acute mediastinitis appears as mediastinal widening, pneumomediastinum, obliteration of fat planes, localized fluid collections, and abscess formation. Patients with mediastinitis are often very ill, presenting with fever, chills, tachycardia, chest pain, and elevated white blood cell counts. Sternal infection is frequently associated with deeper mediastinal infection, and sternal dehiscence is frequently associated with osteomyelitis of the sternum (11).
In our group, noninfectious and infectious events involving the chest wall accounted for 10 of 89 complications. Two patients developed sternal dehiscence, one 10 days and the other 17 months after transplantation (Fig 19). The latter patient received a direct blow to the chest from a truck door. Both patients survived the acute episode, with the first patient requiring sternal débridement and muscle flap reconstruction for bacterial wound infection and pleuromediastinosternal cutaneous fistula (Fig 20).
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Figure 19a. Sternal dehiscence in a 52-year-old man who sustained blunt chest trauma 17 months after cardiac transplantation. (a) CT scan shows distraction of sternal fragments. (b) CT scan obtained inferior to a shows anterior fluid collection consistent with resolving hematoma.
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Figure 19b. Sternal dehiscence in a 52-year-old man who sustained blunt chest trauma 17 months after cardiac transplantation. (a) CT scan shows distraction of sternal fragments. (b) CT scan obtained inferior to a shows anterior fluid collection consistent with resolving hematoma.
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Figure 20a. Pleuromediastinal cutaneous fistula in a 51-year-old man who developed coagulase-negative staphylococcal sternal wound infection 10 days after cardiac transplantation. (a) CT scan shows subcutaneous emphysema in the left chest wall. (b) Nonenhanced CT scan obtained inferior to a shows air in the sternal dehiscence and in infiltrated anterior mediastinal fat, findings consistent with infection. (c) CT scan obtained inferior to b shows more extensive pneumomediastinum and a right pneumothorax.
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Figure 20b. Pleuromediastinal cutaneous fistula in a 51-year-old man who developed coagulase-negative staphylococcal sternal wound infection 10 days after cardiac transplantation. (a) CT scan shows subcutaneous emphysema in the left chest wall. (b) Nonenhanced CT scan obtained inferior to a shows air in the sternal dehiscence and in infiltrated anterior mediastinal fat, findings consistent with infection. (c) CT scan obtained inferior to b shows more extensive pneumomediastinum and a right pneumothorax.
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Figure 20c. Pleuromediastinal cutaneous fistula in a 51-year-old man who developed coagulase-negative staphylococcal sternal wound infection 10 days after cardiac transplantation. (a) CT scan shows subcutaneous emphysema in the left chest wall. (b) Nonenhanced CT scan obtained inferior to a shows air in the sternal dehiscence and in infiltrated anterior mediastinal fat, findings consistent with infection. (c) CT scan obtained inferior to b shows more extensive pneumomediastinum and a right pneumothorax.
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Five patients developed substernal fluid collections, requiring débridement (n = 3) and aspiration (n = 2), between 2 days and 7 months (mean, 2.5 months) after transplantation (Figs 21, 22). All five survived the acute episode, but two patients died 2 and 3 years later of accelerated coronary artery atherosclerosis.
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Figure 21a. Figures 21, 22. (21) Mediastinal abscess in a 62-year-old man who developed a substernal fluid collection 6 weeks after cardiac transplantation. (a) Lateral chest radiograph reveals retrosternal air bubbles (arrows) and a moderate left pleural effusion. (b) Contrast-enhanced CT scan shows the anterior mediastinal loculated fluid collection with air pockets. Specimen obtained from CT-guided drainage revealed gram-positive cocci, and the patient responded to antibiotic therapy and drainage. (22) Mediastinal abscess in a 55-year-old man who developed a candidal incisional infection requiring rectus abdominis muscle flap reconstruction, recurrent débridements, and antifungal therapy. (a) Nonenhanced CT scan reveals a small retrosternal fluid collection with air bubbles (arrow) and left pleural effusion. (b) Nonenhanced CT scan obtained 6 months later shows anterior rectus abdominis muscle flap (arrow), sternal dehiscence, and residual retrosternal fluid.
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Figure 21b. Figures 21, 22. (21) Mediastinal abscess in a 62-year-old man who developed a substernal fluid collection 6 weeks after cardiac transplantation. (a) Lateral chest radiograph reveals retrosternal air bubbles (arrows) and a moderate left pleural effusion. (b) Contrast-enhanced CT scan shows the anterior mediastinal loculated fluid collection with air pockets. Specimen obtained from CT-guided drainage revealed gram-positive cocci, and the patient responded to antibiotic therapy and drainage. (22) Mediastinal abscess in a 55-year-old man who developed a candidal incisional infection requiring rectus abdominis muscle flap reconstruction, recurrent débridements, and antifungal therapy. (a) Nonenhanced CT scan reveals a small retrosternal fluid collection with air bubbles (arrow) and left pleural effusion. (b) Nonenhanced CT scan obtained 6 months later shows anterior rectus abdominis muscle flap (arrow), sternal dehiscence, and residual retrosternal fluid.
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Figure 22a. Figures 21, 22. (21) Mediastinal abscess in a 62-year-old man who developed a substernal fluid collection 6 weeks after cardiac transplantation. (a) Lateral chest radiograph reveals retrosternal air bubbles (arrows) and a moderate left pleural effusion. (b) Contrast-enhanced CT scan shows the anterior mediastinal loculated fluid collection with air pockets. Specimen obtained from CT-guided drainage revealed gram-positive cocci, and the patient responded to antibiotic therapy and drainage. (22) Mediastinal abscess in a 55-year-old man who developed a candidal incisional infection requiring rectus abdominis muscle flap reconstruction, recurrent débridements, and antifungal therapy. (a) Nonenhanced CT scan reveals a small retrosternal fluid collection with air bubbles (arrow) and left pleural effusion. (b) Nonenhanced CT scan obtained 6 months later shows anterior rectus abdominis muscle flap (arrow), sternal dehiscence, and residual retrosternal fluid.
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Figure 22b. Figures 21, 22. (21) Mediastinal abscess in a 62-year-old man who developed a substernal fluid collection 6 weeks after cardiac transplantation. (a) Lateral chest radiograph reveals retrosternal air bubbles (arrows) and a moderate left pleural effusion. (b) Contrast-enhanced CT scan shows the anterior mediastinal loculated fluid collection with air pockets. Specimen obtained from CT-guided drainage revealed gram-positive cocci, and the patient responded to antibiotic therapy and drainage. (22) Mediastinal abscess in a 55-year-old man who developed a candidal incisional infection requiring rectus abdominis muscle flap reconstruction, recurrent débridements, and antifungal therapy. (a) Nonenhanced CT scan reveals a small retrosternal fluid collection with air bubbles (arrow) and left pleural effusion. (b) Nonenhanced CT scan obtained 6 months later shows anterior rectus abdominis muscle flap (arrow), sternal dehiscence, and residual retrosternal fluid.
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One patient developed a large pneumomediastinum 4 days after transplantation, related to a persistent air leak (Fig 23). The lung had been injured at surgery, secondary to extensive dissection of multiple adhesions. The patient was treated successfully with mediastinal chest tube placement.
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Figure 23a. Pneumomediastinum in a 63-year-old man who developed extensive subcutaneous emphysema 4 days after cardiac transplantation. (a) AP upright chest radiograph shows right anterior pneumomediastinum (arrows) and left subcutaneous emphysema. (b) CT scan shows anterior mediastinal and bilateral subcutaneous air collections. The patient underwent mediastinal chest tube placement and recovered.
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Figure 23b. Pneumomediastinum in a 63-year-old man who developed extensive subcutaneous emphysema 4 days after cardiac transplantation. (a) AP upright chest radiograph shows right anterior pneumomediastinum (arrows) and left subcutaneous emphysema. (b) CT scan shows anterior mediastinal and bilateral subcutaneous air collections. The patient underwent mediastinal chest tube placement and recovered.
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In two patients, a sternal wire protruded through the skin, requiring surgical removal, 4 months and 5 years after transplantation (Fig 24). Both survived the surgery, but one patient died 2 months later of gram-negative sepsis.
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Figure 24. Sternal wire protrusion in a 34-year-old man that developed 17 months after cardiac transplantation. Contrast-enhanced CT scan reveals the tip of a sternal wire (arrow) protruding through the anterior skin surface (arrowheads) and right pleural effusion. The wire was surgically removed and the patient recovered.
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Bleeding Complications
Mediastinal bleeding requiring reexploration has been reported in about 9% of cardiac transplant patients (39). Ten of our 232 patients returned to the operating room for reexploration to control bleeding. Bleeding sites included aortic anastomosis (n = 3), right atrial anastomosis (n = 1), and sternal edges (n = 1). In six patients, the sites were not specified, and one patient was bleeding from both the right atrial and aortic anastomoses (Fig 25). Three patients died despite reexploratio
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Abstract
INTRODUCTION
