- Email: [email protected]
Cardiac hemangiosarcoma in the dog: Therapeutic considerations
VOLUME 19 ISSUE 2 FEBRUARY 2006
Advances in Small Animal Medicine and Surgery Cardiac Hemangiosarcoma in the Dog: Therapeutic Considerations William E. Herndon DVM, Diplomate ACVIM (Cardiology) California Veterinary Specialists 100 N. Rancho Santa Fe Rd., STE 133 San Marcos, CA 92069 Pericardial effusion is a relatively common cause of cardiac disease in dogs, especially large breeds.1-6 The accumulation of a sufficient amount of fluid within the pericardial sac results in a limitation of diastolic filling. Although both sides of the heart are affected, the thinner walls of the right ventricle are more easily compressed than the left ventricle as intrapericardial pressure increases. Echocardiographic signs of pericardial tamponade (e.g., early diastolic collapse of the right ventricular free wall and late diastolic to early systolic collapse of the right atrium) usually indicate at least a 20% decrease in cardiac output and is often accompanied by clinical signs. Clinical signs of pericardial tamponade include anorexia, lethargy, collapse, tachypnea, and vomiting. Physical examination findings may include pale mucous membranes, jugular distention, paradoxical pulses (weaker on inspiration), tachycardia, muffled heart sounds, abdominal effusion, weakness, recumbency, and depression. Common causes of pericardial effusion in dogs include neoplasia (hemangiosarcoma, chemodectoma, and mesothelioma are the most common), idiopathic effusion, and infection. Cardiac hemangiosarcoma is the single most common cause of pericardial effusion in the dog, comprising approximately half of all cases.1-6 Large studies investigating rational therapy following diagnosis of symptomatic cardiac hemangiosarcoma are limited. Although it would seem appropriate to remove all or a portion of the pericardium in such cases in order to prevent
future episodes of pericardial tamponade, to my knowledge, this has not been shown to be effective at prolonging the diseasefree interval or prolonging survival for the average dog.4 This may be due to the highly metastatic nature of the disease, or because a hemothorax rather than just cardiac tamponade occurs following tumor hemorrhage.
“Cardiac hemangiosarcoma is the single most common cause of pericardial effusion in the dog.” Chemotherapy alone without removing macroscopic disease is not considered to be an effective treatment for hemangiosarcoma. Consequently, the recent publication by Weisse and colleagues provides unique and clinically relevant information about the treatment of cardiac hemangiosarcoma.7 In this retrospective multi-center study, the case records of 23 dogs with histopathologically confirmed right atrial hemangiosarcoma were evaluated to determine if surgical removal of the tumor with or without adjuvant chemotherapy affected survival. Also, the authors evaluated morbidity and mortality associated with these therapies. The following itemize some of the important findings from the publication by Weisse and colleagues7 followed by editorial comments (in italics):
1. Mean age was 9.1 years (median 9.1), range 3.2 to 13.5 years. Although one commonly thinks of hemangiosarcomas afflicting geriatric patients, younger dogs may also have cardiac hemangiosarcoma. 2. Vomiting was reported as a presenting clinical sign in 7 of 23 dogs (30%). Vomiting can be a clinical sign of pericardial tamponade in dogs. This has also been shown in a recently completed large retrospective study.6 3. A low platelet count was present in 5 dogs (24%). Although thrombocytopenia is considered relatively common in dogs with splenic hemangiosarcoma, it is not consistently present in dogs with cardiac hemangiosarcoma.
Advances
Page 2
4. Results of thoracic radiographs were available for 21 dogs. No evidence of pulmonary metastatic disease was noted. Only 1 dog was determined to have pulmonary metastatic disease based on visual inspection of the lungs at the time of surgery. Previous reports have identified higher metastatic rates when evaluated at surgery, even though thoracic radiographs may not show evidence of metastasis. Many dogs with cardiac hemangiosarcoma will succumb to metastatic disease, regardless whether or not it was grossly evident at the time of diagnosis. 5. Eleven of 23 dogs (48%) had cardiac masses identified by means of echocardiography.7 The authors cite previous publications stating the echocardiographic sensitivity in detecting a cardiac mass is 14% and 17%, respectively. Echocardiography is both user and equipment dependent. Given the nature of the study, it is impossible to determine the level of training of the clinician performing the echocardiogram. Also, one of the studies cited by the authors was published in 1984. Veterinary echocardiography was juvenile in its development in 1984. Further-
more, current ultrasound technology has dramatically improved over the last 10 to 15 years. When a cardiologist performs the echocardiogram, a cardiac mass has been shown to be present 70% (61 of 87 cases) of the time.6 It is recommended, when possible (e.g., a hemodynamically stable patient), that an echocardiogram be performed when pericardial fluid is present. This allows for better visualization of masses, if present. 6. Pericardial fluid pH was more than 7.0 in 5 of 6 dogs in the present study,7 supporting findings of a previous study in which pericardial fluid pH more than 7.0 was identified in 39 of 42 (93%) animals with neoplasia. Although pericardial fluid pH in 5 of 6 dogs in the paper7 did support a diagnosis of neoplasia based on a previous publication8 (alkaline pH suggesting neoplastic etiology), such findings could not be reproduced in a study of 37 dogs.9 Evaluation of pericardial fluid supernatant with a portable pH meter did not discriminate between neoplastic and non-neoplastic causes.9 In fact, overlap of pericardial fluid pH occurred in 33 of 37 (89%) cases. Furthermore, there was no statistical dif-
ference in the median pericardial fluid pH in the study.9 Another study of 23 dogs with pericardial effusion suggested that idiopathic effusions had a more alkaline pH than neoplastic cases.10 Therefore, I do not recommend that pericardial fluid pH be used to help differentiate neoplastic from non-neoplastic causes of pericardial effusion. 7. Eighty-seven percent of dogs were discharged from the hospital. The median time from surgery to discharge was 3 days (19 dogs). Only one dog developed vomiting and diarrhea, presumably associated with doxorubicin administration. This seems to indicate that neither surgical removal of the tumor and pericardium nor chemotherapy was associated with significant mortality or morbidity. 8. All dogs in the study had atrial tumor removal. The median survival for the 8 dogs (35%) who also received adjuvant chemotherapy was 175 days. The median survival for the 15 dogs (65%) treated with surgery alone was 42 days. These findings suggest that surgical removal of cardiac hemangiosarcoma with follow up chemotherapy was associated with prolonged survival. Survival in those dogs treated with
Advances surgery alone was similar to previous studies of cardiac hemangiosarcoma, regardless of the type of therapy. Such comparisons, however dramatic they may be, are based on historical comparison of previously published reports and do not represent the findings of prospective, blinded, and placebo controlled study (as the authors mention). However, the results suggest that cardiac hemangiosarcoma be treated, when possible, similarly to splenic hemangiosarcoma (i.e., surgical removal with follow up chemotherapy). In conclusion, careful diagnosis of cardiac hemangiosarcoma (usually based on anatomic location of a mass noted on echocardiography) is important when considering the prognosis and therapy of dogs with pericardial effusion. Also, this publication highlights the utility of multicenter data base collection. Such data, on a large scale, would be particularly useful in veterinary cardiology. REFERENCES 1. Ehrhart N, Ehrhart EJ, Willis J, et al. Analysis of factors affecting survival in dogs with aortic body tumors. Vet Surg 2002;31:44-48. 2. Stepien RL, Whitley NT, Dubielzig RR, et al. Idiopathic or mesothelioma B related pericardial effusion: clinical findings and survival in 17 dogs studied retrospectively. J Small Anim Pract 2000;41:342-327. 3. Aronsohn MG, Carpenter JL. Surgical treatment of idiopathic pericardial effusion in the dog: 25 cases (1978-1993). J Am Anim Hosp Assoc 1999;35:521-525. 4. Dunning D, Monnet E, Orton CE, et al. Analysis of prognostic indicators for dogs with pericardial effusion: 46 cases (19851996). J Am Vet Med Assoc 1998;212: 1276-1280. 5. Kerstetter KK, Krahwinkel DJ, Millis DL, et al. Pericardectomy in dogs: 22 cases (1978-1994). J Am Vet Med Assoc 1997; 211:736-740. 6. Tobias A, Jacob K, Fine D, et al. Pericardial disorders: 87 cases of pericardial effusion in dogs (January 1, 1999 To December 31, 2001). ACVIM Forum 2002. 7. Weisse C, Soares N, Beal MW, et al. Survival times in dogs with right atrial hemangiosarcoma treated by means of surgical resection with or without adjuvant chemotherapy: 23 cases (1986-2000). J Am Vet Med Assoc 2005;226:575-579. 8. Edwards NJ. The diagnostic value of pericardial fluid pH determination. J Am Anim Hosp Assoc 1996;32:63-67. 9. Fine DM, Tobias AH, Jacob KA, et al. Use of pericardial fluid pH to distinguish between idiopathic and neoplastic effusions. J Vet Intern Med 2003;17:525-529.
Page 3
10. de Laforcade AM, Rozanski EA, Freeman LM, et al. Biochemical analysis of pericardial fluid and whole blood in 23 dogs. International Veterinary Emergency and Critical Care Symposium, 7th annual. 2000, p. 802.
Advances in Small Animal Medicine and Surgery Cardiac Hemangiosarcoma in the Dog: Therapeutic Considerations William E. Herndon DVM, Diplomate ACVIM (Cardiology) California Veterinary Specialists 100 N. Rancho Santa Fe Rd., STE 133 San Marcos, CA 92069 Pericardial effusion is a relatively common cause of cardiac disease in dogs, especially large breeds.1-6 The accumulation of a sufficient amount of fluid within the pericardial sac results in a limitation of diastolic filling. Although both sides of the heart are affected, the thinner walls of the right ventricle are more easily compressed than the left ventricle as intrapericardial pressure increases. Echocardiographic signs of pericardial tamponade (e.g., early diastolic collapse of the right ventricular free wall and late diastolic to early systolic collapse of the right atrium) usually indicate at least a 20% decrease in cardiac output and is often accompanied by clinical signs. Clinical signs of pericardial tamponade include anorexia, lethargy, collapse, tachypnea, and vomiting. Physical examination findings may include pale mucous membranes, jugular distention, paradoxical pulses (weaker on inspiration), tachycardia, muffled heart sounds, abdominal effusion, weakness, recumbency, and depression. Common causes of pericardial effusion in dogs include neoplasia (hemangiosarcoma, chemodectoma, and mesothelioma are the most common), idiopathic effusion, and infection. Cardiac hemangiosarcoma is the single most common cause of pericardial effusion in the dog, comprising approximately half of all cases.1-6 Large studies investigating rational therapy following diagnosis of symptomatic cardiac hemangiosarcoma are limited. Although it would seem appropriate to remove all or a portion of the pericardium in such cases in order to prevent
future episodes of pericardial tamponade, to my knowledge, this has not been shown to be effective at prolonging the diseasefree interval or prolonging survival for the average dog.4 This may be due to the highly metastatic nature of the disease, or because a hemothorax rather than just cardiac tamponade occurs following tumor hemorrhage.
“Cardiac hemangiosarcoma is the single most common cause of pericardial effusion in the dog.” Chemotherapy alone without removing macroscopic disease is not considered to be an effective treatment for hemangiosarcoma. Consequently, the recent publication by Weisse and colleagues provides unique and clinically relevant information about the treatment of cardiac hemangiosarcoma.7 In this retrospective multi-center study, the case records of 23 dogs with histopathologically confirmed right atrial hemangiosarcoma were evaluated to determine if surgical removal of the tumor with or without adjuvant chemotherapy affected survival. Also, the authors evaluated morbidity and mortality associated with these therapies. The following itemize some of the important findings from the publication by Weisse and colleagues7 followed by editorial comments (in italics):
1. Mean age was 9.1 years (median 9.1), range 3.2 to 13.5 years. Although one commonly thinks of hemangiosarcomas afflicting geriatric patients, younger dogs may also have cardiac hemangiosarcoma. 2. Vomiting was reported as a presenting clinical sign in 7 of 23 dogs (30%). Vomiting can be a clinical sign of pericardial tamponade in dogs. This has also been shown in a recently completed large retrospective study.6 3. A low platelet count was present in 5 dogs (24%). Although thrombocytopenia is considered relatively common in dogs with splenic hemangiosarcoma, it is not consistently present in dogs with cardiac hemangiosarcoma.
Advances
Page 2
4. Results of thoracic radiographs were available for 21 dogs. No evidence of pulmonary metastatic disease was noted. Only 1 dog was determined to have pulmonary metastatic disease based on visual inspection of the lungs at the time of surgery. Previous reports have identified higher metastatic rates when evaluated at surgery, even though thoracic radiographs may not show evidence of metastasis. Many dogs with cardiac hemangiosarcoma will succumb to metastatic disease, regardless whether or not it was grossly evident at the time of diagnosis. 5. Eleven of 23 dogs (48%) had cardiac masses identified by means of echocardiography.7 The authors cite previous publications stating the echocardiographic sensitivity in detecting a cardiac mass is 14% and 17%, respectively. Echocardiography is both user and equipment dependent. Given the nature of the study, it is impossible to determine the level of training of the clinician performing the echocardiogram. Also, one of the studies cited by the authors was published in 1984. Veterinary echocardiography was juvenile in its development in 1984. Further-
more, current ultrasound technology has dramatically improved over the last 10 to 15 years. When a cardiologist performs the echocardiogram, a cardiac mass has been shown to be present 70% (61 of 87 cases) of the time.6 It is recommended, when possible (e.g., a hemodynamically stable patient), that an echocardiogram be performed when pericardial fluid is present. This allows for better visualization of masses, if present. 6. Pericardial fluid pH was more than 7.0 in 5 of 6 dogs in the present study,7 supporting findings of a previous study in which pericardial fluid pH more than 7.0 was identified in 39 of 42 (93%) animals with neoplasia. Although pericardial fluid pH in 5 of 6 dogs in the paper7 did support a diagnosis of neoplasia based on a previous publication8 (alkaline pH suggesting neoplastic etiology), such findings could not be reproduced in a study of 37 dogs.9 Evaluation of pericardial fluid supernatant with a portable pH meter did not discriminate between neoplastic and non-neoplastic causes.9 In fact, overlap of pericardial fluid pH occurred in 33 of 37 (89%) cases. Furthermore, there was no statistical dif-
ference in the median pericardial fluid pH in the study.9 Another study of 23 dogs with pericardial effusion suggested that idiopathic effusions had a more alkaline pH than neoplastic cases.10 Therefore, I do not recommend that pericardial fluid pH be used to help differentiate neoplastic from non-neoplastic causes of pericardial effusion. 7. Eighty-seven percent of dogs were discharged from the hospital. The median time from surgery to discharge was 3 days (19 dogs). Only one dog developed vomiting and diarrhea, presumably associated with doxorubicin administration. This seems to indicate that neither surgical removal of the tumor and pericardium nor chemotherapy was associated with significant mortality or morbidity. 8. All dogs in the study had atrial tumor removal. The median survival for the 8 dogs (35%) who also received adjuvant chemotherapy was 175 days. The median survival for the 15 dogs (65%) treated with surgery alone was 42 days. These findings suggest that surgical removal of cardiac hemangiosarcoma with follow up chemotherapy was associated with prolonged survival. Survival in those dogs treated with
Advances surgery alone was similar to previous studies of cardiac hemangiosarcoma, regardless of the type of therapy. Such comparisons, however dramatic they may be, are based on historical comparison of previously published reports and do not represent the findings of prospective, blinded, and placebo controlled study (as the authors mention). However, the results suggest that cardiac hemangiosarcoma be treated, when possible, similarly to splenic hemangiosarcoma (i.e., surgical removal with follow up chemotherapy). In conclusion, careful diagnosis of cardiac hemangiosarcoma (usually based on anatomic location of a mass noted on echocardiography) is important when considering the prognosis and therapy of dogs with pericardial effusion. Also, this publication highlights the utility of multicenter data base collection. Such data, on a large scale, would be particularly useful in veterinary cardiology. REFERENCES 1. Ehrhart N, Ehrhart EJ, Willis J, et al. Analysis of factors affecting survival in dogs with aortic body tumors. Vet Surg 2002;31:44-48. 2. Stepien RL, Whitley NT, Dubielzig RR, et al. Idiopathic or mesothelioma B related pericardial effusion: clinical findings and survival in 17 dogs studied retrospectively. J Small Anim Pract 2000;41:342-327. 3. Aronsohn MG, Carpenter JL. Surgical treatment of idiopathic pericardial effusion in the dog: 25 cases (1978-1993). J Am Anim Hosp Assoc 1999;35:521-525. 4. Dunning D, Monnet E, Orton CE, et al. Analysis of prognostic indicators for dogs with pericardial effusion: 46 cases (19851996). J Am Vet Med Assoc 1998;212: 1276-1280. 5. Kerstetter KK, Krahwinkel DJ, Millis DL, et al. Pericardectomy in dogs: 22 cases (1978-1994). J Am Vet Med Assoc 1997; 211:736-740. 6. Tobias A, Jacob K, Fine D, et al. Pericardial disorders: 87 cases of pericardial effusion in dogs (January 1, 1999 To December 31, 2001). ACVIM Forum 2002. 7. Weisse C, Soares N, Beal MW, et al. Survival times in dogs with right atrial hemangiosarcoma treated by means of surgical resection with or without adjuvant chemotherapy: 23 cases (1986-2000). J Am Vet Med Assoc 2005;226:575-579. 8. Edwards NJ. The diagnostic value of pericardial fluid pH determination. J Am Anim Hosp Assoc 1996;32:63-67. 9. Fine DM, Tobias AH, Jacob KA, et al. Use of pericardial fluid pH to distinguish between idiopathic and neoplastic effusions. J Vet Intern Med 2003;17:525-529.
Page 3
10. de Laforcade AM, Rozanski EA, Freeman LM, et al. Biochemical analysis of pericardial fluid and whole blood in 23 dogs. International Veterinary Emergency and Critical Care Symposium, 7th annual. 2000, p. 802.