Arteriovenous Fistulae Secondary to Renal Cell Carcinoma Clinical and Cardiovascular Manifestations : Report of a Case By

A 63-year-old woman presented with progressive congestive heart failure and unexplained cardiomegaly. Diagnostic workup revealed large arteriovenous fistulae in the lower pole of the left kidney. A total left nephrectomy was performed and microscopic exam revealed renal cell carcinoma. Following surgery, the congestive heart failure cleared and the patient -has been asymptomatic for one year. The pertinent findings of the 22 patients who have been reported previously in the literature with arteriovenous fistulae complicating renal cell carcinoma are reviewed. Thirty percent of the patients presented with cardiovascular complaints, and 60% had significant cardiovascular findings during the course of evaluation. An abdominal bruit was the most discriminating finding on physical exam, and it occurred in 72% of the reported cases. The diagnosis was unexpectedly established by surgery in 13%, and by angiography in 87% usually in the course of a workup for hypertension, abdominal pain, hematuria, or during search for an occult malignancy. An extensive evaluation is required for early diagnosis of this correctible cause of hypertension and heart failure.

ARTERIOVENOUS FISTULAE may occur from a variety of causes, and the cardiovascular effects of the altered circulatory state have been well described in the literature.1 2 Renal cell carcinoma with significant arteriovenous shunt formation is an uncommonly encountered entity,3-19 yet it is a reversible cause of hypertension and heart failure. 9 We recently had the opportunity of seeing a patient with chronic, severe congestive heart failure secondary to arteriovenous fistulae complicating an unsuspected renal cell carcinoma. The case is being reported and the available English literature reviewed in order to summarize the clinical and cardiovascular manifestations of this disease entity. M.L. (SMH #82-41-48) is a 63-year-old woman who was admitted to the Strong Memorial Hospital on October 7, 1972, with congestive heart failure and pulmonary edema. She had no history of hypertension, valvular heart disease or chest pain. Cardiovascular exam revealed a blood pressure of 175/80 mm Hg, pulse regular at 110 per minute, distended jugular veins, diffuse pulmonary rales, cardiomegaly without heart murmurs, and pitting pre-tibial edema. Routine laboratory studies were unremarkable including a urinanalysis without gross or microscopic hematuria. She responded to digoxin, diuretics, oxygen, and low salt diet. During the course of this hospitalization a systolic bruit was heard over the left flank, but the patient refused an intravenous pyelogram for further evaluation. Twelve days after admission she was discharged in a markedly improved condition.
During the subsequent year, she developed progressive congestive heart failure despite an augmented cardiac regimen. She was readmitted on November 21, 1973, with congestive heart failure and a very rapid ventricular response to atrial fibrillation. Cardiac examination revealed a well-nourished woman with a blood pressure of 180/75 mm Hg, an irregular pulse at 130 per minute, a normal thyroid gland, elevated jugular venous pressure, and congestive rales. Cardiomegaly was present with enlargement of the heart to the anterior axillary line; the first heart sound was accentuated, a right ventricular heave was palpable, and a grade 2/6 ejection-type systolic murmur was heard   performed. auici the ivinous blond above the renil veinis had an oxx gen saturation h5% higher thatin that beloss these vessels (table 1) Oi lDecember 10, 1 973 a totAl left rnephrectomin wx as performed. (Cit section of the remoxivedl kidniex rexvealed an irregulair loblulated tuiirior in the lower pole xwith n) icentifiable caipstule; mnicroscopic exam of this area showed at i-enal cell carcirnuna of the grade 11  Abbreviations: CHF = congestive heart failure; HBP = sigii = absent; NR = not reported. high blood pressure; plus sign = present; minus others, or as simply present in the remaining patients in which it was recorded. In contrast to what might be expected, a palpable abdominal mass or hematuria was reported in less than 50% of the patients. Patients with this condition were generally in the older age group (70% greater than 50 years of age), and the striking preponderance of women (70%) is unexplained. The diagnosis of renal cell carcinoma with arteriovenous fistulae was rarely made on initial clinical exam. The diagnosis was unsuspectingly established by surgery in 13% and by angiography in 87%, usually in the course of a workup for hypertension, abdominal pain, hematuria, or during search for an occult malignancy.

Discussion
Our patient presented with unexplained congestive heart failure, and clinically, an atypical atrial myxoma was suspected. High cardiac output and a left-to-right shunt were documented at cardiac catheterization, and renal arteriovenous fistulae were demonstrated angiographically. Etiologic considerations of the latter  finding include congenital angiomatosis with multiple arteriovenous connections, and acquired lesions due to trauma, renal biopsy, inflammation, arteriosclerosis, or renal cell carcinoma.2 Our patient is quite typical of the clinical picture which has evolved from a review of the literature. That is, the patient is a female in the older age group and presented with cardiovascular symptoms. Significant cardiovascular abnormalities were detected on exam including a systolic abdominal bruit, but the clinical diagnosis was not entertained by numerous physicians who examined the patient. There was no abdominal mass or hematuria, and the angiographic findings of renal cell carcinoma with arteriovenous fistulae were quite unexpected. Certain angiographic criteria have been established to differentiate large arteriovenous fistulae from the small shunts which are commonly seen in most cases of renal cell carcinoma. Bosniak categorized renal arteriovenous fistulae as large when considerable opacification of the renal vein occurs within one second following opacification of the renal artery, or if renal vein and aorta opacify while there is still contrast medium within the aorta.2' The normal opacification of the inferior vena cava occurs approximately eight seconds after aortic injection, whereas it occurs in four-to-five seconds in patients with large arteriovenous fistulae.
Circulatory effects of renal arteriovenous fistulae are similar to fistulae between other vessels of similar size.' 2 The markedly reduced peripheral resistance is associated with a shortened circulation time, an augmented cardiac output, and an elevated systolic blood pressure. Secondary effects include an increase in the blood volume, venous pressure, heart rate, and progressive right and left sided cardiac enlargement from the systemic venous and arterial volume overload. Diastolic hypertension, which occurs in approximately one-half the reported cases, is thought to Circulation, Volume 52, August 1975 result from "renalvascular steal' with renal parenchymal ischemia on the side of the fistulae.2 5 , 18 The over-all cardiovascular manifestations of the arteriovenous fistulae are dependent on: 1) the magnitude of the shunt as determined by the size of the feeding artery and draining vein and by the level of systemic blood pressure; 2) the chronicity of the fistulae; and 3) the status of the cardiovascular system prior to the development of the fistulae. Thus, one could expect a spectrum of cardiovascular symptoms and signs in this condition as a result of variability in the severity of the aforementioned factors.
There is a paucity of reported data on quantitation of the left-to-right shunt in arteriovenous fistulae complicating renal cell carcinoma. Curtiss et al.'8 reported one patient with a 1.23:1 shunt flow and minimal hemodynamic embarassment. In our patient, sufficient data were not obtained to quantitate the shunt flow; however, it was estimated from the indicator dilution curves, the magnitude of the venous oxygen step up above the renal veins, and the angiographic findings that the shunt was greater than 2:1.
The formation of fistulae in renal cell carcinoma involves multiple connections between arteries and veins due to tumor invasion and the development of communicating vascular spaces within partially necrotic tumor. Although these arteriovenous fistulae are most marked in the primary carcinoma, similar fistulae have been reported in metastatic implants of renal cell carcinoma. [22][23][24][25][26] The sparsity of arteriovenous fistulae in other types of malignancy suggests some unique characteristics in the local growth and invasive properties of renal cell carcinoma.
It is quite obvious that total nephrectomy of the involved kidney is the treatment of choice if local tumor extension does not preclude surgery. Even if metastatic lesions exist, and especially if they are solitary, nephrectomy may be indicated to eliminate the hemodynamic burden of the arteriovenous fistulae. The short-term follow-up results of surgical nephrectomy have been excellent from a cardiovascular standpoint with improvement in the congestive heart failure and reduction or normalization of the blood pressure. The long-term results are determined by the growth characteristics of the renal cell carcinoma.