(Chest. 2002;122:1096-1098.)
© 2002
American College of Chest Physicians
Effects of Continuous IV Prostacyclin in a Patient With Pulmonary Veno-occlusive Disease*
Hiroyuki Okumura, MD;
Noritoshi Nagaya, MD;
Shingo Kyotani, MD;
Fumio Sakamaki, MD;
Norifumi Nakanishi, MD;
Shinya Fukuhara, MD and
Chikao Yutani, MD
* From the Departments of Internal Medicine (Drs. Okumura, Nagaya, Kyotani, Sakamaki, and Nakanishi) and Pathology (Drs. Fukuhara and Yutani), National Cardiovascular Center, Osaka, Japan.
Correspondence to: Noritoshi Nagaya, MD, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan; e-mail: nagayann{at}hsp.ncvc.go.jp
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Abstract
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Pulmonary veno-occlusive disease (PVOD) is a rare but life-threatening disease. Although prostacyclin (PGI2) attenuates pulmonary hypertension and improves the prognosis in patients with primary pulmonary hypertension, little information is available regarding the effect of PGI2 on patients with PVOD. This report describes a patient with severe PVOD who showed marked improvement in exercise capacity and pulmonary hemodynamics with continuous IV PGI2 treatment. Furthermore, he experienced no clinical events for 12 months and survived for 25 months after the initiation of PGI2 therapy. These results suggest that continuous IV PGI2 therapy may serve as a bridge to transplantation in some cases of PVOD.
Key Words: prostacyclin • pulmonary veno-occlusive disease
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Introduction
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Pulmonary veno-occlusive disease (PVOD) describes the disease in a subset of patients with pulmonary hypertension histologically characterized by fibrotic occlusion of the smaller pulmonary veins. PVOD is an uncommon form of unexplained pulmonary hypertension that is rarely diagnosed during life and is generally associated with a progressively deteriorating course. In most cases, PVOD is refractory to medical treatment and patients require transplantation, although occasional instances of favorable responses to some agents have been reported.1
2
Continuous IV administration of prostacyclin (PGI2) has been established as a treatment for primary pulmonary hypertension (PPH).3
4
However, the effect of PGI2 on PVOD remains unclear. We report on a patient with PVOD who showed marked improvement in exercise capacity, pulmonary hemodynamics, and probably prognosis after PGI2 therapy was initiated.
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Case Report
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A 30-year-old man with New York Heart Association functional class IV was hospitalized with chief complaints of syncope and dyspnea, which had begun in November 1998. He had no medical or family history of note. He had smoked one pack of cigarettes per day for 10 years. He was noted to have jugular vein dilatation, a loud pulmonary component of S2, an S3 gallop, right ventricular lift, and hepatomegaly. Arterial blood gas analysis (room air) revealed a pH of 7.45, PO2 of 66.0 mm Hg, and PCO2 of 26.7 mm Hg. The ECG showed right ventricular hypertrophy. The chest radiograph revealed prominent pulmonary arteries and interstitial shadows in the right lower lung field, indicating pulmonary congestion. The results of a workup for secondary causes of pulmonary hypertension were normal. Pulmonary function tests showed reduced diffusing capacity of the lung for carbon monoxide (40.0% of predicted). Ventilation-perfusion images revealed normal ventilation and diffuse focal areas of hypoperfusion. Right heart catheterization revealed severe pulmonary arterial hypertension (mean pulmonary arterial pressure, 70 mm Hg; pulmonary vascular resistance, 15.1 Wood U; mean right atrial pressure, 17 mm Hg; pulmonary capillary wedge pressure, 10 mm Hg; cardiac output, 3.97 L/min). Ischemic heart disease, valvular disease, and cardiomyopathy were excluded by echocardiography and cardiac catheterization. Based on these findings and the presence of pulmonary congestion, PVOD, a subtype of PPH, was strongly suspected. Continuous IV PGI2 was immediately begun at 1 ng/kg/min and was progressively titrated by 10 ng/kg/min in a week, because the patient’s general condition deteriorated critically. Thereafter, the PGI2 dosage was gradually increased by 1 ng/kg/min per week. Two episodes of pulmonary edema occurred during follow-up. However, the patient’s symptoms and chest radiographic findings were significantly improved when the dose of PGI2 was titrated to 29 ng/kg/min. Furthermore, his 6-min walk distance increased from 90 to 450 m, and his mean pulmonary artery pressure decreased from 70 to 36 mm Hg. He was discharged from the hospital about 4 months after the start of PGI2 administration.
Although the patient returned to work and was employed in desk work, he was rehospitalized about 12 months after discharge. His general condition worsened despite intensive care. Finally, his respiratory state deteriorated, and marked interstitial shadows appeared in the chest radiograph and CT scan (Fig 1
). We tried several agents, such as prednisolone, dobutamine, diuretics, and nitric oxide inhalation, but the patient died of respiratory failure about 2 years after the initiation of continuous IV PGI2.
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Figure 1.. Top: chest radiograph shows significant interstitial shadows. Bottom: chest CT scan shows diffuse alveolar shadows in bilateral lower lung fields. These findings suggest pulmonary edema.
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At autopsy, gross examination of the lungs revealed severe pulmonary edema. Histologic sections from the lungs demonstrated the typical changes of PVOD. Diffuse stenosis of the pulmonary veins and venules by fibrous tissue, thickened media of the veins, and interstitial edema resulted in a thickening of the lobular septa, engorged and tortuous alveolar capillaries, and hemosiderosis in every section. Pulmonary arterioles exhibited severe medial hypertrophy, but plexiform lesions were absent (Fig 2
). The final clinical diagnosis of PVOD was made from these autopsy findings.
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Figure 2.. Top left: section of lung shows occlusion of a small pulmonary vein. Alveolar walls are significantly thickened due to interstitial edema (Masson trichrome, original x400). Top right: alveolar capillaries are so engorged and tortuous as to resemble pulmonary capillary hemangiomatosis. Hemosiderin-laden macrophages are present in the same section (hematoxylin-eosin, original x200). Bottom left: Elastica van Gieson stain demonstrates arterialized pulmonary veins (original x400). Bottom right: lobular septa are significantly thickened due to interstitial edema, and pleural lymphatics are dilated (hematoxylin-eosin, original x100).
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Discussion
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Although PGI2 therapy has been established as a treatment for PPH, the use of this treatment for PVOD, a subtype of PPH, is controversial. There are theoretical reasons about why PGI2 may not be efficacious in patients with PVOD and why it may, in fact, worsen the cardiopulmonary status. If the pulmonary arterioles dilate but the resistance of the pulmonary veins remains fixed, an increase in transcapillary hydrostatic pressure may ensue and produce florid pulmonary edema.5
6
Thus, lung transplantation is thought to be the only therapy that improves the prognosis in patients with PVOD.
In this case, however, we successfully administered continuous IV PGI2, and observed its long-term effect on patients with PVOD. Continuous IV PGI2 markedly improved the symptoms, exercise capacity, and hemodynamics in a patient with PVOD, resulting in relatively long-term survival. Holcomb et al7
showed that continuous IV PGI2 had beneficial effects in 3 of 11 patients with PVOD. These findings suggest that some patients with PVOD respond well to therapy with IV PGI2. An experimental study8
has demonstrated that PGI2 dilates not only pulmonary arteries but also pulmonary veins in the porcine model. Furthermore, short-term administration of PGI2 has been reported9
to reverse the increased vasomotor tone in pulmonary venules in a patient with PVOD. Thus, it is interesting to speculate that in this case, the administration of PGI2 played a role in the regulation of vascular tone in pulmonary venules rather than in pulmonary arteries. In addition, careful dose adjustments and maintenance of PGI2 may have contributed to the favorable clinical outcome in this patient.
In conclusion, PGI2 therapy may have beneficial effects in some patients with PVOD and thereby may serve as a bridge to transplantation.
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Footnotes
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Abbreviations: PGI2 = prostacyclin; PPH = primary pulmonary hypertension; PVOD = pulmonary veno-occlusive disease
Received for publication February 27, 2002.
Accepted for publication April 24, 2002.
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References
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- Chawla, SK, Kittel, CF, Faber, LP, et al (1976) Pulmonary veno-occlusive disease. Ann Thorac Surg 22,249-253[Abstract]
- Sanderson, JE, Spiro, SG, Hardry, AT, et al A case of pulmonary veno-occlusive disease responding to treatment with azathioprine. Thorax 1977;32,140-148[Abstract]
- Rich, S, Kaufmann, E, Levy, PS The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. N Engl J Med 1992;327,76-81[Abstract]
- Barst, RJ, Rubin, LJ, McGoon, MD, et al A comparison of continuous intravenous epoprostenol (PGI2) with conventional therapy for primary pulmonary hypertension: the Primary Pulmonary Hypertension Study Group. N Engl J Med 1996;334,296-302[Abstract/Free Full Text]
- Palmer, SM, Robinson, LJ, Wang, A, et al Massive pulmonary edema and death after prostacyclin infusion in a patient with pulmonary veno-occlusive disease. Chest 1998;113,237-240[Abstract/Free Full Text]
- Mandel, J, Mark, EJ, Hales, CA Pulmonary veno-occlusive disease. Am J Respir Crit Care Med 2000;162,1964-1973[Free Full Text]
- Holcomb, BW, Loyd, JE, Ely, EW, et al Pulmonary veno-occlusive disease: a case series and new observations. Chest 2000;118,1671-1679[Abstract/Free Full Text]
- Greenberg, S Effect of prostacyclin and 9a, 11a-epoxymethanoprostaglandin H2 on calcium and magnesium fluxes and tension development in canine intralobar pulmonary arteries and veins. J Pharmacol Exp Ther 1981;219,326-337[Abstract/Free Full Text]
- Davis, LL, deBoisblanc, BP, Glynn, CE, et al Effect of prostacyclin on microvascular pressures in a patient with pulmonary veno-occlusive disease. Chest 1995;108,1754-1756[Abstract/Free Full Text]
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Abstract
Introduction
