Approach Considerations
Specific PAH therapies may be associated with a risk of pulmonary edema at any time during the therapy. Extreme caution should be used while administering intravenous or subcutaneous prostanoids and dose escalation should be relatively slow.
No well-structured, prospective clinical trials have been performed to evaluate the effect of various nonsurgical interventions on the outcome of pulmonary veno-occlusive disease (PVOD). Currently, the information gained from clinical trials involving other forms of pulmonary arterial hypertension (PAH) is extrapolated from clinical experience, case reports, and case series in order to choose various therapies. Patients with PVOD are best served at a pulmonary hypertension specialty center.
No general consensus has been reached on the choice of first-line therapy for persons with PVOD. However, because PAH therapies (eg, continuous intravenous prostacyclin) are poorly tolerated and are perceived to have only a marginal effect on outcome, patients are offered the option of lung transplantation whenever possible. In the absence of this surgery, most patients do not survive beyond 2-3 years after diagnosis.
Lung transplantation
Currently, lung transplantation is the only therapeutic option capable of significantly prolonging and improving the lives of patients with PVOD. [49] Single- and double-lung transplantation procedures have both been used. Recurrence after heart-lung transplantation was reported in one patient. [50]
Specific PAH Therapies
The use of specific pulmonary arterial hypertension (PAH) therapies—eg, prostacyclin analogues, endothelin receptor antagonists, phosphodiesterase-5 inhibitors—in patients with pulmonary veno-occlusive disease (PVOD) is controversial.
Initial reports described the development of acute fulminant pulmonary edema and death [51] in association with infusions of intravenous epoprostenol. A 2008 report comparing PVOD patients with or without PCH to idiopathic patients reported pulmonary edema in 7 of 16 PVOD patients with vasodilator therapy. [52] However, in patients who do not have the option of lung transplantation, PVOD results in death within a few months to years after diagnosis. Consequently, continuous intravenous epoprostenol has been tried in PVOD patients, very cautiously and with relatively slow-dose up-titration. This treatment was met with some success. [47]
Epoprostenol has been reported to have some beneficial effects on hemodynamics in patients with pulmonary veno-occlusive disease (PVOD) and it has been demonstrated to reverse the increased vasomotor tone in pulmonary venules. [53] However, no structured clinical trials are available to support the use of any specific PAH therapies in PVOD patients.
Presently, treatment must be individualized to the patient after discussing the risks and benefits from the sparse data available. Pulmonary edema may occur, acutely or months after initiation of therapy, with the use of vasodilators. [39]
In the absence of an obvious or potential contraindication, the American College of Chest Physicians recommends anticoagulation in patients with PAH. [54] It is not unreasonable to consider anticoagulation with warfarin (Coumadin) in PVOD patients if they have no contraindications (eg, history of significant hemoptysis). The target international normalized ratio (INR) is 1.5-2.5.
Long-term oxygen supplementation therapy should be used for hypoxemic patients with PVOD to keep their oxyhemoglobin saturation at greater than 90% at all times. This may result in symptomatic and subjective improvement. No direct good-quality evidence exists for speculation about the magnitude of benefit in terms of survival or exercise capacity in patients with PVOD.
Immunosuppressants, Steroids, and Antithrombotic Agents
Other therapies have been reported to have some role in pulmonary veno-occlusive disease (PVOD) management. However, their use is not widespread.
The role of immunosuppressive medications in the treatment of PVOD remains undefined but these agents may help a subset of patients with PVOD, particularly those with autoimmune features. [31]
A trial of corticosteroids may be considered following a chest radiograph and oxygen therapy. Although it does not change the course of the disease, corticosteroid treatment may provide symptomatic improvement. [55]
Most experimental interventions involve antithrombotic treatment with agents such as heparin, thrombolytic agents such as recombinant tissue plasminogen activator, antithrombin III concentrate in patients with a documented antithrombin III deficienc. Another drug, defibrotide, which is a polydeoxyribonucleotide derived from mammalian cells, is now approved in the United States for hepatic VOD in adults and children with renal or pulmonary dysfunction following HSCT. Currently, none of these therapies has any role in the treatment of patients with PVOD.
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Medium-power photomicrograph (original magnification, X10; hematoxylin and eosin stain) demonstrates a fibrotic interlobular septum containing a vein with an occluded lumen (arrowhead). The occlusion is composed of dense, collagen-rich, fibrous tissue. Image courtesy of Thoracic Imaging Section, Department of Radiologic Pathology, Armed Forces Institute of Pathology.
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Pulmonary veno-occlusive disease in a 43-year-old man. An axial computed tomography (CT) scan (lung window level) shows multiple septal lines (arrowhead) and a dilated central pulmonary artery (arrow). Image courtesy of Thoracic Imaging Section, Department of Radiologic Pathology, Armed Forces Institute of Pathology.
Tables
Features |
Pulmonary Edema |
PVOD |
Chest radiograph |
|
|
Kerley B lines |
Present |
Present |
Pleural effusion |
Usually present |
May be present |
Enlarged cardiac silhouette |
Present |
Less prominent |
Enlarged pulmonary artery |
Present |
Present |
Chest CT scan |
|
|
Thickened septae |
Present |
Present |
Pleural effusion |
Usually present |
May be present |
Enlarged heart |
Present |
Less prominent |
Enlarged pulmonary artery |
Present |
Present |
Septal concavity into left ventricle |
Absent |
Present |
Echocardiogram |
|
|
Pulmonary artery systolic pressure |
Elevated (usually not >80 mm Hg) |
Elevated (may be >80 mm Hg) |
Left atrial enlargement |
Present |
Absent |
Right atrial enlargement |
Present |
Present |
Right ventricular hypertrophy |
Absent |
Present |
Paradoxical septal motion |
Absent |
Present |
Large pericardial effusion |
Absent |
May be present |
Right-sided heart catheterization |
|
|
Pulmonary vascular resistance |
Below 3.0 Wood units |
Above 3.0 Wood units |
Pulmonary capillary wedge pressure |
Above 18 mm Hg |
Usually below 15 mm Hg (if catheter is properly wedged) |
Mean pulmonary artery pressure |
Elevated (almost never >50 mm Hg) |
Elevated (may be >50 mm Hg) |
Cardiac output |
May be normal, low, or high |
Mostly decreased, may be low normal |
Oxyhemoglobin step-up |
Absent |
Absent |
