Abstract: Case Reports |


Manica Sodhi, MD*; Omar Minai, MD; Hina Sahi, MD
Author and Funding Information

Cleveland Clinic, Cleveland, OH


Chest. 2008;134(4_MeetingAbstracts):c15001. doi:10.1378/chest.134.4_MeetingAbstracts.c15001
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INTRODUCTION: Vascular endothelial growth factor (VEGF) plays a central role in the maintenance, differentiation and function of endothelial cells. It has been demonstrated in animal models that VEGF receptor blockade causes severe pulmonary hypertension associated with pre-capillary arterial occlusion by proliferating endothelial cells 1. Bevacizumab, a recombinant humanized anti-VEGF monoclonal antibody is approved by the United States Food and Drug Administration (FDA) for cancer treatment. We present the case of a patient who developed severe pulmonary hypertension while on treatment with bevacizumab for ovarian cancer.

CASE PRESENTATION: A 65 year-old Caucasian woman with a medical history of diabetes mellitus type 2, hypertension, hyperlipidemia, hypothyroidism and metastatic ovarian cancer, initially underwent neo-adjuvant chemotherapy with paclitaxel and carboplatin before undergoing extensive surgery. After surgery, numerous chemotherapeutic agents were used to induce remission, including intraperitoneal carboplatin, doxorubicin, tamoxifen, gemcitabine. Finally, due to a lack of response, bevacizumab and cyclophosphamide regimen was initiated. Eighteen months after intiation of bevacizumab, the patient presented with gradually worsening dyspnea. Echocardiogram, which was previously normal, revealed an ejection fraction of 55% and new finding of severely dilated right ventricle with an estimated right ventricular systolic pressure (RVSP) of 81 mm Hg. CT scan of the chest was negative for any parenchymal or vascular disease. Ventilation-perfusion lung scan showed a low probability for a pulmonary embolism. ×-natriuretic peptide level was 268 pg/ml. She had no history of liver disease, anorexigen use, and HIV testing was negative. Right heart catheterization revealed a pulmonary artery mean pressure (mPAP) of 52 mm Hg, occlusion pressure (PAOP) of 12 mm Hg, vascular resistance (PVR)-8 Wood units and cardiac index of 2.16 l/min/m2. Suspecting bevacizumab induced pulmonary hypertension, bevacizumab was discontinued and sildenafil 20 mg three times daily started. Unfortunately, her dyspnea and hypoxemia continued to worsen, despite increasing the dose of sildenafil. Right heart catheterization, six weeks later, revealed increased mPAP to 80 mm Hg and PVR to 21 Wood units with decreased cardiac index to 1.13 l/min/m2. With invasive hemodynamic monitoring sildenafil was increased to 80 mg TID, and inhaled iloprost initiated. Lack of hemodynamic response prompted initiation of intravenous epoprostenol. However, the patient's condition continued to deteriorate, ultimately leading to her demise.

DISCUSSIONS: VEGF inhibitors are being increasingly used today for treatment of metastatic colorectal cancer; non-squamous, non-small cell lung cancer; metastatic breast cancer, ovarian cancer, renal cell cancer and age-related macular degeneration. In a trial of bevacizumab for ovarian cancer, two of the seventy patients developed pulmonary hypertension; however this was not reported to be severe or fatal 2. Severe pulmonary hypertension in our patient was attributable to treatment with bevacizumab. This pulmonary hypertension showed lack of response to conventional therapy and was rapidly progressive.

CONCLUSION: To the best of our knowledge, this is the first report of severe fatal pulmonary hypertension attributable to vascular endothelial growth factor inhibitor use. With increasing use of these agents, we advocate increased awareness of this potential life threatening complication. Serial echocardiograms and other appropriate investigative modalities should be undertaken at the earliest sign or symptom suggestive of development of pulmonary hypertension.

DISCLOSURE: Manica Sodhi, No Financial Disclosure Information; No Product/Research Disclosure Information

Monday, October 27, 2008

4:15 PM - 5:45 PM


Am J Physiol Lung Cell Mol Physiol2002;283:555–562. [CrossRef]
J Clin Oncol.2008;26(1):76–82. [CrossRef]




Am J Physiol Lung Cell Mol Physiol2002;283:555–562. [CrossRef]
J Clin Oncol.2008;26(1):76–82. [CrossRef]
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