Acquired Pericardial Effusions: Specific Causes, Epidemiology, Treatment, and Prognosis

By | 2013-06-11

Idiopathic Pericardial Effusion

Idiopathic pericardial effusion is a diagnosis of exclusion. It is made in cases with pericardial effusion where no intrapericardial masses are identified after thorough echocardiographic evaluation and the results of ancillary tests, such as pericardial fluid analysis, fail to disclose a cause. Pericardial histopathology and immunohistochemistry from dogs with idiopathic pericardial effusion demonstrate extensive pericardial fibrosis and a mixed inflammatory response of greatest intensity at the cardiac surface of the tissue. Perivascular lymphoplasmacytic aggregates are present at the pleural surface within the fibrosed pericardium. No vascular pathology or deposition of immunoglobulin or complement within the vessel wall exists, suggesting that the pericarditis is not due to a vasculitis. Immunohistochemistry findings are consistent with a predominandy humoral immune response, but they do not support a primary immune-mediated pathogenesis. The factor or factors that initiate idiopathic pericarditis remain unknown.

As with any diagnoses of exclusion, a diagnosis of idiopathic pericardial effusion should be made with appropriate caution. Small intrapericardial tumors may elude detection, especially in cases where echocardiography is performed after pericardiocentesis. In addition, mesothelioma is a diffuse neoplasm of the pericardium and other serosal surfaces, and it does not result in appreciable thickening of the pericardium on echocardiography. Cytology of pericardial effusion cannot distinguish between idiopathic pericardial effusion and mesothelioma. Consequendy, mesothelioma should always be considered as an important differential diagnosis for idiopathic pericardial effusion. Idiopathic pericardial effusion has not been reported in cats

Idiopathic pericardial effusion was diagnosed in eight of 42 dogs (19%) with pericardial effusion in a retrospective study from the Veterinary Teaching Hospital, Colorado State University. Idiopathic pericardial effusion was provisionally diagnosed in 24 of 87 dogs with pericardial effusion at the University of Minnesota Veterinary Medical Center from January 1999 to December 2001, but mesothelioma was eventually confirmed in four of these cases. Consequently, 20 of 87 cases (23%) with pericardial effusion in the University of Minnesota Veterinary Medical Center study population were finally diagnosed as having idiopathic pericardial effusion, which is similar to the data from Colorado State University. Average age among the cases with idiopathic pericardial effusion in the University of Minnesota Veterinary Medical Center study population was 94 years (±2.2 years), average weight was 28.9 kg (±14.5 kg), and there was no apparent sex predisposition (11 males:9 females). Five of the 20 dogs (25%) were golden retrievers, and the breed was over-represented (odds ratio, 4.2; 95% confidence interval, 1.6 to 11.2).

The initial treatment for idiopathic pericardial effusion is pericardiocentesis to remove as much pericardial fluid as possible. The author’s preferred approach is to restrain the animal in left lateral recumbency and to approach the pericardium from the right side ().

The gross appearance of pericardial fluid is usually indistinguishable from blood. To confirm that the catheter is in the pericardial space, an aliquot of fluid is placed in an ACT tube. Blood will normally clot in an ACT tube within 60 to 90 seconds. In contrast, sanguineous effusions in body cavities are rapidly depleted of clotting factors and thrombocytes, and pericardial fluid will consequendy not clot. If no clots form within the activated clotting tube after 3 to 5 minutes, all of pericardial fluid is aspirated and samples are collected for fluid analysis and culture. The catheter is then removed.

In virtually all cases with pericardial effusion, pericardiocentesis results in rapid and marked hemodynamic improvement. Clinical signs, pulse quality, and mucous membrane perfusion improve, and heart rate decreases. However, ventricular and supraventricular arrhythmias (including atrial fibrillation) are common after pericardiocentesis. These arrhythmias seldom require therapy and usually resolve spontaneously. The author prefers to hospitalize and monitor cases for 12 to 24 hours after pericardiocentesis.

The author usually treats an initial episode of idiopathic pericardial effusion by pericardiocentesis alone, followed by pericardiectomy in cases that develop recurrent effusions. Recurrent effusions, effusive-constrictive, and constrictive pericarditis are well-recognized complications after pericardiocentesis in cases with idiopathic pericardial effusion. Among the 20 cases diagnosed with idiopathic pericardial effusion in the University of Minnesota Veterinary Medical Center study population, six died or were euthanized after developing recurrent effusions with tamponade within 44 days of their initial episode. Cardiac tamponade with pulmonary thromboembolism was the cause of death in one dog. Postmortem examinations were not performed in the remaining five cases, and the possibility that some dogs might have had cardiac tumors that eluded detection during echocardiography cannot be excluded. Among the remaining 14 dogs, four developed recurrent effusions necessitating pericardiectomy, and a further six developed effusive-constrictive pericarditis between 3 months and 3 years after their initial episode. Median survival time (MST) among the 20 cases was 663 days, indicating a generally good prognosis in cases with idiopathic pericardial effusion. However, the complication rate among these cases was high, and this is consistent with the results of others.

The complication rate among cases with idiopathic pericardial effusion would probably be lower if pericardiectomy was performed at the time of the initial episode rather than after recurrent effusion. Pericardiectomy would avoid the risk of recurrent life-threatening cardiac tamponade and the potential for developing effusive-constrictive and constrictive pericarditis. In addition, surgery permits examination of thoracic and intrapericardial structures to rule out other causes of pericardial effusion, including tumors and foreign bodies. Although pericardiectomy is by no means devoid of morbidity and mortality, it is an extremely successful procedure for idiopathic pericardial effusion. Consequendy, it is likely that pericardiectomy will increasingly form part of the initial treatment for cases with idiopathic pericardial effusion, especially as minimally invasive methods for the procedure become more widespread.

Colchicine, nonsteroidal anti-inflammatories, and corticosteroids are prescribed for humans with recurrent idiopathic pericarditis. Colchicine and nonsteroidal anti-inflammatories are recommended in most cases, and the use of corticosteroids is limited to very severe cases. Colchicine for the treatment of recurrent pericarditis in humans is promising, although data from large controlled prospective studies are lacking. The safety and efficacy of colchicine, nonsteroidal anti-inflammatories, corticosteroids, and any other medical therapies in the management of idiopathic pericardial effusion in small animals have yet to be established.

Mesothelioma

Mesothelioma is emerging as an increasingly important cause of pericardial effusion. Mesothelioma was confirmed in four of 87 dogs (5%) in the University of Minnesota Veterinary Medical Center study population of dogs with pericardial effusion. Average age among the affected cases at time of presentation was 9.5 years (±2.2 years), average weight was 37.5 kg (± 11.1 kg), and males and females were equally represented. No breed predisposition has been reported, and affected breeds in the University of Minnesota Veterinary Medical Center population were Akita, golden retriever, Labrador retriever, and springer spaniel. Mesothelioma causing pericardial effusion has been described in a cat, but pericardial mesothelioma is rare in this species.

The clinical course of pericardial effusion due to mesothelioma in the University of Minnesota Veterinary Medical Center study population followed a characteristic pattern. Presenting and clinical signs were no different from other cause of pericardial effusion. In all four cases, a provisional diagnosis of idiopathic pericardial effusion was made after various diagnostic procedures, including echocardiography and pericardial fluid analysis failed to disclose a cause for the pericardial effusion. Pericardiocentesis was performed, and this was repeated at 77 days (± 46 days) when the dogs developed recurrent effusions with tamponade. Pericardiectomies were then performed in all cases; histopathology of the excised pericardia was consistent with idiopathic pericarditis in three cases, and mesothelioma in one. Severe and unremitting pleural effusions requiring repeated thoracocentesis began at 103 days (±44 days) after pericardiectomy. Intracavitary cisplatin was administered in two dogs, but this did not appear to signifi-candy change the course of the disease. Thoracocentesis was necessary every 2 to 3 weeks until death or euthanasia, and MST from the initial episode of pericardial effusion was 312 days (range, 206 to 352). In all cases, mesothelioma that had spread throughout the thoracic cavity was confirmed on postmortem examination.

The signalment and clinical course among cases with pericardial effusion due to mesothelioma in the University of Minnesota Veterinary Medical Center study population are strikingly similar to those described by others. It is extremely difficult to distinguish between idiopathic pericardial effusion and pericardial effusion due to mesothelioma, even with pericardial histopathology and immunohistochemistry. The clinical course of the disease is suggestive, and accumulation of significant amounts of pleural effusion within 120 days of pericardiectomy increases the index of suspicion for mesothelioma. In addition to being a diagnostic challenge, mesothelioma is difficult to treat. However, long-term survival has been reported in a dog in which a histopathologic diagnosis of pericardial mesothelioma was made after pericardiectomy for recurrent pericardial effusion. Treatment in that case was initiated 48 hours after surgery with intracavitary cisplatin and intravenous doxoru-bicin, and the dog was free of disease 27 months later. Intracavitary cisplatin has successfully resolved pleural effusions in some dogs with pleural mesothelioma.

Cardiac Hemangiosarcoma

In a retrospective study from the Veterinary Teaching Hospital, Colorado State University, cardiac hemangiosarcoma was diagnosed in 14 of 42 dogs (33%) with pericardial effusion. At the UMVMC, cardiac hemangiosarcoma was diagnosed either by echocardiography or echocardiography and histopathology in 53 of 87 dogs (61%) in the study population with pericardial effusion. Cardiac hemangiosarcoma with pericardial effusion was nearly three times more prevalent than the second most common form of pericardial effusion, idiopathic pericardial effusion. Average age among the affected dogs was 9.8 years (± 2.1 years), and their average weight was 32.0 kg (± 12.2 kg). Males slightly outnumbered females (31 males:22 females), but the difference was not statistically significant when compared with the general hospital population. Sixteen of the 57 dogs (28%) were golden retrievers and the breed was over-represented (odds ratio, 5.3; 95% confidence interval, 2.9 to 9.4).

Two features of these data suggest that important changes have occurred in the epidemiology of cardiac hemangiosarcoma. First, the prevalence of cardiac hemangiosarcoma in the University of Minnesota Veterinary Medical Center study population was nearly twice that of the Colorado State University study population. The reasons for this are not clear; however, regional differences in the epidemiology of cardiac hemangiosarcoma may exist, or the prevalence of the disease may have increased over time. Second, the golden retriever was the only over-represented breed among the cases with cardiac hemangiosarcoma in the University of Minnesota Veterinary Medical Center study population. Cardiac hemangiosarcoma has previously been recognized most frequendy in German shepherds. More recendy, cardiac hemangiosarcoma has also been seen commonly in golden retrievers at the Veterinary Hospital, University of Pennsylvania.

Treatment for all forms of hemangiosarcoma is challenging, and a diagnosis of cardiac hemangiosarcoma confers a grave prognosis. By the time of diagnosis, cardiac hemangiosarcoma usually has metastasized and should be considered a systemic disease. At the UMVMC, the majority of owners of dogs with cardiac hemangiosarcoma elect to have their dogs treated by peri-cardiocentesis alone on one or more occasions. Pericardiocentesis is predictably associated with marked clinical improvement, but clinical signs of tamponade typically recur within a few days, often resulting in death or prompting euthanasia. In the University of Minnesota Veterinary Medical Center study population, MST among dogs with cardiac hemangiosarcoma treated by pericardiocentesis alone (n = 30) was just 11 days (range, 0 to 208). Percutaneous balloon peri-cardiotomy has been described in the dog, and the procedure may provide longer periods of palliation in cases with cardiac hemangiosarcoma.

More aggressive approaches to the treatment of cardiac hemangiosarcoma include various combinations of pericardiectomy, tumor resection, splenectomy in cases with splenic metastases, and chemotherapy. Survival data for cases managed in this manner are limited. In a case report of right atrial hemangiosarcoma treated with chemotherapy alone, survival time was 20 weeks. In dogs treated by surgery alone (tumor resection and pericardiectomy or creation of a pericardial window, or pericardiectomy alone), reported survival times range from 2 days to 8 months.. No survival data are available that compare surgery alone, with surgery and chemotherapy for dogs with cardiac hemangiosarcoma. Further, no compelling evidence suggests that survival times in dogs with either splenic or cardiac hemangiosarcoma can be significantly prolonged with adjuvant chemotherapy. Nevertheless, the management of cardiac hemangiosarcoma should always involve consultation with an oncologist to take advantage of continually emerging modalities for the treatment of this highly malignant tumor.

Heart Base Tumors

The majority of heart base tumors in dogs are aortic body tumors. English bulldogs, boxers, and Boston terriers are predisposed, although aortic body tumors also occur in nonbrachycephalic breeds. In various studies, brachycephalic breeds have accounted for between 39% and 85% of dogs with aortic body tumors. Chronic hypoxia induces hyperplasia and neoplasia of chemoreceptors, which may explain the predisposition of brachycephalic breeds to aortic body tumors. Among the predisposed breeds, males may be at increased risk for developing aortic body tumors, but differences in sex predisposition are not statistically significant in all studies.. The age range at time of diagnosis of aortic body tumors is 6 to 15 years with an average of 10 years. Between 5% and 10% of tumors at the heart base are ectopic thyroid tumors. Aortic body tumors are reported in cats, but they are rare in this species.

Most aortic body tumors are benign and locally expansive, although local invasiveness and metastases occur in both dogs and cats. Two studies report metastases mosdy to the lungs and liver in approximately 10% to 12% of dogs with aortic body tumors. In a third study, 58% (14 of 24) of aortic body tumors were benign, 25% (6 of 24) were locally invasive, and 21% (5 of 24) were metastatic. Sites of metastases included the lungs, left atrium, pericardium, and kidneys. The biologic behavior of ectopic thyroid tumors at the heart base is less well described, and both ectopic thyroid adenomas and adenocarcinomas with metastases have been reported.

Heart base tumors were diagnosed either by echocardiography or echocardiography and histopathology in six dogs among the 87 cases (7%) with pericardial effusion in the University of Minnesota Veterinary Medical Center study population. Affected breeds were Great Dane, Labrador retriever, German shorthaired pointer, boxer, English springer spaniel, and Old English sheepdog. Average age was 11.1 years (±2.2 years), and average weight was 31.4 kg (± 13.0 kg). One dog was male and five were female. The number of dogs with heart base tumors in the University of Minnesota Veterinary Medical Center study population is small, but the epidemiologic data are reasonably in accord with those of others, with the exception of sex distribution. The prevalence of heart base tumors is consistent with a recent review of the epidemiology of cardiac tumors in dogs. In that study, aortic body tumors were approximately tenfold less common than cardiac hemangiosarcoma.

Complete surgical resection of heart base tumors is seldom possible because the tumors are highly vascular, located close to major blood vessels, and usually extensive by the time of diagnosis. However, palliation with pericardiectomy either alone or in combination with tumor resection often results in prolonged survival with an excellent quality of life. No evidence indicates that adjuvant chemotherapy improves the prognosis for dogs with heart base tumors. In a recent retrospective study in dogs with aortic body tumors in which surgery was performed, the following factors were evaluated for effect on survival time: sex; breed; presence or absence of respiratory distress; the presence of an arrhythmia other than respiratory sinus arrhythmia; the presence of pleura), pericardia), or peritoneal effusion; evidence of pulmonary metastases; treatment with pericardiectomy; and treatment with chemotherapy. No attempt was made to achieve turnorfree margins in the dogs in that study. Among the various factors evaluated, only treatment with pericardiectomy had a significant effect on survival, and the survival advantage was remarkable. MST among dogs after pericardiectomy was 730 days, whereas those that did not have a pericardiectomy had a MST of only 42 days.

Other Causes of Acquired Pericardia! Effusion

Bacterial, fungal, and viral infections are occasionally associated with pericardial effusions in small animals. Most cases of pericardial effusions due to bacterial infections are thought to arise as a consequence of intrapericardial foreign body penetration, usually by migrating foxtails (Hordeum spp.). Foxtail migration is a common and often serious problem in the western United States. Bacterial pericarditis has also been described in a puppy after a dog bite and in a young adult dog after thoracic trauma. In contrast to most other causes of pericardial effusion, pericardial fluid cytology and culture is crucial in the diagnosis of septic cases. In the largest series of infectious pericardial effusion reported in dogs (five cases), treatment involved pericardiectomy and removal of any foreign bodies, chest drainage, and antibiotic therapy for up to 6 months. All dogs recovered without complications, suggesting that dogs with bacterial pericarditis have a good prognosis when treated aggressively with a combination of surgical and medical therapy.

Systemic coccidioidomycosis in dogs has been associated with pericardial disease. In most cases the fungal infection results in effusive-constrictive or constrictive pericarditis. Coccidioidomycosis should be considered, especially in dogs with pericardial disease that reside in or have a travel history that includes areas where the soil fungus Coccidioides immitis is endemic, such as the Southwestern United States. Treatment involves pericardiectomy, chest drainage, and antifungal therapy (usually beginning with Amphotericin B). Based on limited published information and experience, the prognosis for cases of coccidioidomycosis with pericardial involvement is poor. A case of effusive-constrictive pericarditis due to Aspergillus niger has been reported in a dog.

FIP is one of the more common diseases associated with pericardial effusion in the cat. Pericardial effusions that are occasionally voluminous are present in some cats suffering from this systemic and invariably fatal viral disease.

Left atrial rupture is an uncommon cause of pericardial effusion that occurs in smaller breed dogs with chronic degenerative disease of the mitral valve. Affected cases show clinical signs of acute tamponade, and a loud left apical murmur is usually apparent despite muffling of the heart sounds. Echocardiography discloses intrapericardial fluid, a mass caudal to the left ventricle due to thrombus formation, and substantial mitral regurgitation. Pericardiocentesis is immediately necessary in most cases. Further, the possibility of continued hemorrhage exists, necessitating blood transfusion and emergency thoracotomy to remove larger clots from the pericardial space and to repair the left atrium. The prognosis in such cases is grave.

Cardiac lymphosarcoma and rhabdomyosarcoma with pericardial effusion have been reported in both dogs and cats, but these are rare. Among the various cardiac tumors, cardiac lymphosarcoma is unique because cytology of the pericardial fluid establishes the diagnosis in many cases, and the tumor is amenable to combination chemotherapy.

Pericardial effusions secondary to coagulation disorders rarely result in clinically significant tamponade. However, a case of pericardial effusion and cardiac tamponade secondary to anticoagulant rodenticide toxicity has been reported in a dog. Pericardial effusions secondary to disseminated intravas-cular coagulation, warfarin toxicity, and other coagulopathies have been reported in cats.

Pericardial effusion is frequendy detected in cases with congestive heart failure in small animals, but usually not in sufficient quantity to cause significant hemodynamic compromise. Pericardial effusion secondary to uremia has been recognized in both dogs and cats.