Superior Vena Cava Syndrome
Superior vena cava (SVC) syndrome is the clinical manifestation of SVC obstruction and occurs through external compression, thrombosis, or invasion of the vein. While previously in the realm of nonneoplastic entities such as syphilitic aortitis or histoplasmosis, SVC syndrome is now almost exclusively (>90%) secondary to malignancy.1 The syndrome complicates 2% to 8% of primary thoracic malignancies, most frequently small cell carcinoma of the lung, followed by other lung cancer histologies, non-Hodgkin's lymphoma, and mediastinal germ cell tumors.2–5 Studies estimate the risk of clinically evident subclavian vein thrombosis to be approximately 5%6,7 in cancer patients with indwelling central venous catheters, and some small percentage of these apparently evolve to SVC syndrome.8–10
To understand the clinical manifestations of the syndrome, an appreciation of the regional anatomy is necessary (Fig. 72-1). Because the venous drainage from the upper extremities, upper thorax, and head is obstructed, SVC syndrome presents with symptoms related to engorgement of these areas. Both the degree of SVC compromise and the extent of collateral veins determine the varied clinical presentation, which can be as mild as slight facial and upper extremity edema or as dire as intracranial swelling, seizures, hemodynamic instability, and tracheal obstruction. Table 72-2 lists the frequency of symptoms in 66 patients admitted with SVC obstruction.1 Because of the lore of the dire symptomatologies, physicians often react to suspected SVC syndrome with panicked urgency and are tempted to initiate treatment before a pathologic diagnosis can be made. However, some argue convincingly that the SVC syndrome is rarely so urgent as to preclude timely and methodical radiologic and pathologic evaluations prior to therapy.11
Table 72–2. Presenting Symptoms and Signs of SVC Obstruction in 66 Patients ||Download (.pdf)
Table 72–2. Presenting Symptoms and Signs of SVC Obstruction in 66 Patients
|Face Swelling||83||Neck Vein Distention||92|
|Cough||70||Arm Vein Distention||68|
|Orthopnea||64||Upper Extremity Swelling||64|
|Nasal Stuffiness||35||Mentation Changes||27|
|Blackout||3||Upper Body Plethora||3|
Frontal (left) and lateral (right) sections of the thorax depicting the anatomic structures adjacent to the SVC. The shaded area indicates the most common site of obstruction in SVC syndrome.
When a patient presents with suspected SVC syndrome, the first step is to obtain an imaging study to both confirm the diagnosis and assist in treatment decisions. Of the several imaging modalities available for diagnosing the syndrome, the best study is the one that can be obtained most expediently. Magnetic resonance imaging (MRI), contrast-enhanced computed tomographic (CT) scanning, radionuclide flow study, and traditional venography are all adequate modalities, but at most centers CT scan is the most readily available. CT scan and MRI also provide information regarding possible etiologies and thus can direct the approach to a tissue diagnosis. The approach to establishing a tissue diagnosis is defined by both the patient's clinical stability and the findings on examination and radiographic studies. Table 72-3 summarizes the diagnostic yields for several tests ranging from noninvasive approaches such as sputum cytology to the maximally invasive thoracotomy. Tissue diagnoses are important because they guide treatment; specifically, they identify patients for whom SVC syndrome should be treated with combination chemotherapy rather than with local measures such as radiation therapy or percutaneous vascular procedures. Patients with known thoracic malignancies clearly do not require a further tissue diagnosis.
Table 72–3. Diagnostic Yield of Various Tests in SVC Syndrome ||Download (.pdf)
Table 72–3. Diagnostic Yield of Various Tests in SVC Syndrome
|Lymph node biopsy||67|
|Bone marrow biopsy||23|
Treatment of SVC syndrome is divided into supportive and definitive therapy. Acutely, patients should be supported with elevation of the head of their bed and supplemental oxygen. Although dexamethasone is sometimes used, its utility has never been supported by experimental data. The definitive treatment of SVC syndrome depends on the etiology. Studies of small cell lung cancer patients with SVC syndrome reveal systemic combination chemotherapy to be more efficacious than radiation therapy, with 73% to 100% of patients experiencing symptomatic relief within 7 days.5,12,13 Conversely, for non-small cell lung cancer and for solid tumors metastatic to the thorax, such as breast cancer, radiation therapy is the preferred treatment modality and is associated with a 56% to 70% success rate within 2 weeks.2 Finally, in patients with non- Hodgkin's lymphoma, single-modality chemotherapy and radiation therapy appear equally efficacious, with 100% of patients experiencing relief of symptoms within 2 weeks.3 For these patients, chemotherapy is argued to be the better modality because it also provides systemic therapy. Patients with recurrent or refractory symptoms may benefit from percutaneous stent placement. SVC stenting with thrombolytic therapy and/or systemic anticoagulation is associated with immediate relief of symptoms in more than 90% of patients and provides excellent palliation in most patients.14–20 Vascular bypass surgery is a treatment modality available for similar patients, but the even higher morbidity and mortality in such patients make it an infrequently employed therapy. Finally, for patients whose SVC syndrome is secondary to venous catheter thrombosis, thrombolytic therapy given within 5 days of the onset of symptoms is associated with a greater than 80% success rate.21,22 For thromboses of longer duration, catheter removal in the setting of systemic anticoagulation with heparin and warfarin may be a more successful approach.
Malignant Pericardial Disease
Pericardial disease in cancer patients can result from a variety of medical conditions, including radiation, uremia, infection, and malignancy. Autopsy series have shown that malignant involvement of the pericardium complicates 5% of cancers and is usually clinically silent.23,24 However, the series reveal that when malignant pericardial disease is symptomatic, it is often the direct or a supporting cause of death. Thoracic tumors are the most frequent tumors to invade the pericardium directly or hematogenously, with lung cancer first, followed by lymphoma and breast cancer.23,24
Malignant pericardial effusion leading to tamponade can be an immediately life-threatening complication of malignant pericardial disease and should be suspected in cancer patients with new cardiopulmonary complaints (see Chap. 28). Because the right-sided cardiac chambers are compressed by surrounding fluid, signs of both right-sided heart failure and left-sided heart insufficiency result. As Table 72-4 details, the presenting symptoms reflect these circulatory disruptions and are, in decreasing order of frequency, dyspnea, cough, orthopnea, chest pain, and pedal edema.25 Examination often reveals hypotension, tachycardia, distended jugular veins, and a paradoxical pulse of greater than 10 mm Hg. Chest radiographs reveal cardiomegaly in most and pleural effusions in approximately half of patients. However, patients with prior chest radiotherapy may not have radiographic evidence of cardiomegaly due to radiation-induced fibrosis of the pericardium. Electrocardiographic (ECG) abnormalities are protean, usually nonspecific, and commonly include sinus tachycardia and decreased voltage in the limb leads but rarely electrical alternans (i.e., alteration in the amplitude of the R wave, as shown in Fig. 72-2).24–26 Echocardiography confirms the diagnosis by revealing effusion associated with inspiratory increase in right ventricular dimensions and right atrial and/or right ventricular collapse. Classically, right-sided heart catheterization reveals equalization of intrapericardial, right atrial, right ventricular diastolic, and pulmonary capillary wedge pressures.27 Since not all pericardial effusions in cancer patients are malignant, both the clinical setting and the results of a diagnostic pericardiocentesis or pericardial biopsy are critical to determining the etiology and therefore the correct treatment for this condition.
Table 72–4. Clinical Presentation of Malignant Pericardial Effusion in 93 Patients ||Download (.pdf)
Table 72–4. Clinical Presentation of Malignant Pericardial Effusion in 93 Patients
|Dyspnea||91||Paradoxical Pulse (>10 mm Hg)||62|
|Orthopnea||32||Tachycardia (>110 beats/min)||43|
|Chest Pain||20||Systolic BP (<110 mmHg)||42|
|Peripheral Edema||17||Respiratory Rate (>20 breaths/min)||35|
|Impaired Level of Consciousness||5||Pericardial Friction Rub||6|
ECG depicting electrical alternans with variation in the amplitude of the QRS complex from beat to beat.
Management of malignant pericardial effusions can be challenging and is divided into temporizing and definitive therapies. The immediate management of a hemodynamically significant pericardial effusion is echocardiography-guided pericardiocentesis. In 97% of patients, the fluid is removed successfully, and symptoms resolve immediately.28 Unfortunately, in approximately 50% of patients, the fluid reaccumulates, requiring subsequent pericardiocenteses. Several more definitive therapies targeted at decreasing the reaccumulation rate have been paired with pericardiocentesis, including radiation therapy, systemic chemotherapy, pericardial sclerotic therapies, and mechanical therapies. When administered following initial pericardiocentesis, these therapies have the following reaccumulation rates: radiation therapy 33%, systemic chemotherapy 30%, pericardial sclerosis with tetracycline 15% to 30%, and mechanical therapies (e.g., indwelling pericardial catheter placement, balloon pericardiotomy, thoracotomy with pericardiostomy) 0% to 15%.29–32
Of all the mechanical therapies, balloon pericardiotomy has the best reaccumulation profile, with 0% to 6% reaccumulation.29–32 The procedure includes a pericardiocentesis followed by balloon catheter dilation of the pericardial needle entrance site. Typically, a balloon catheter is placed across the pericardial entrance site and inflated two to three times, each for 1 to 2 minutes for a total procedure time of 20 to 40 minutes. Side effects have been limited to asymptomatic pleural effusions in most patients.29,30 Not only is balloon pericardiotomy more successful than other less invasive therapies, but it is also the most successful and least morbid of the other mechanical therapies, most of which require general anesthesia and thoracotomy. At centers with staff facile with this technique, patients requiring definitive management of malignant pericardial effusions should be evaluated for this therapy.
Even when fluid does not reaccumulate, cardiac function may not return to normal because of tumor infiltration of the epicardium. This causes diastolic dysfunction mimicking pericardial constriction. This combination of tamponade and cardiac restriction is termed effusive-constrictive pericarditis and may complicate as many as 50% of malignant effusions presenting with hemodynamic compromise. Diagnosis rests on measurement of right side of the heart and pericardial pressures both before and after draining the effusion.33 This complication may lead to critical hemodynamic deterioration in the days following pericardiocentesis, and while some patients may benefit from pericardiectomy, most will succumb.
Radiation-Related Pericardial Disease
Three well-described pericardial syndromes that can
manifest in the months to years following radiation therapy to the mediastinum are acute pericarditis with or without tamponade, pericardial effusion with or without tamponade, and pericardial constriction.34 Such cardiac complications have been described in patients receiving radiation therapy for a variety of tumors within or adjacent to the thoracic cavity (e.g., breast cancer, Hodgkin's disease, esophageal cancer, lung cancer), and one study reported a 9% rate of pericardial effusion in patients receiving radiation therapy to esophageal tumors.35 The authors suggest that effusions may be predictable when considering elements of radiation administration, with fraction sizes of more than 2 Gy associated with increased risk. The symptoms associated with constrictive pericarditis typically develop insidiously over a period of months to years. Increasing abdominal girth and peripheral edema, along with progressive exertional dyspnea, are common complaints. As the disease progresses, symptoms suggestive of cardiac cachexia develop (e.g., weakness, dyspnea at rest, palpitations).
Patients generally have a normal or low blood pressure. Elevated venous pressure is demonstrated by jugular venous distention with a rapid y descent and rapid rebound. In contrast to cardiac tamponade, an inspiratory increase in jugular venous distention (Kussmaul's sign) occurs in constrictive pericarditis. The heart sounds are often distant. Hepatomegaly, pulmonary edema, and ascites are late clinical features of the syndrome. Chest radiographs show an enlarged cardiac silhouette in only slightly more than 50% of cases. Occasionally, intrapericardial calcifications are present; however, the absence of calcifications does not exclude constrictive pericarditis. ECG findings are nonspecific. Atrial fibrillation is observed in long-standing cases owing to elevated atrial pressure.
M-mode and two-dimensional echocardiography can demonstrate pericardial thickening, but most findings are nonspecific. Doppler echocardiography can demonstrate altered patterns of left ventricular filling that distinguish normal individuals from those with constrictive pericarditis. Patients with constrictive pericarditis typically have a rapid deceleration of filling velocity and a shortened filling period.
In constrictive pericarditis, cardiac catheterization will demonstrate equilibration of diastolic pressures in all four chambers. The ventricular pressure tracing will demonstrate the characteristic dip-and-plateau pattern, or square-root sign (Fig. 72-3). The early diastolic dip of ventricular pressure indicates abnormally rapid ventricular filling in constrictive pericarditis. The pulmonary artery pressure is slightly elevated, and the cardiac index is usually decreased. Angiography is able to demonstrate a thickened pericardium in most patients with constrictive pericarditis, and more recently, CT scan has been shown to effectively distinguish between restrictive myocardial disease and constrictive pericarditis by the presence of a thickened pericardium. Clinically significant pericardial effusions are managed with pericardial drainage as described earlier, and pericardial constriction is managed with cardiac surgery (e.g., pericardial stripping, pericardial resection).
Right and left ventricular pressure recording in a patient with constrictive pericarditis. The tracing depicts equilibration of right and left ventricular diastolic pressures and the characteristic square-root sign of the diastolic waveform.