Abstract 12244: 48 Week Outcomes Using Targeted Biologic Inhibition Agents to Treat Aggressive Multivessel Pulmonary Vein Stenosis
Introduction: Intraluminal pulmonary vein stenosis (PVS) can occur in isolation, with congenital heart disease (CHD), chronic lung disease, or both. PVS can progress rapidly with vessel atresia, pulmonary hypertension, and RV failure, and can be fatal within months (mos) of diagnosis. Previous research has demonstrated that intraluminal obstruction occurs due to neointimal proliferation of myofibroblast-like cells, which express VEGF and PDGFR.
Hypothesis: Adjunct targeted inhibition of VEGF (bevacizumab) and PDGFR (imatinib mesylate) may reduce disease activity in patients (pts) with multivessel intraluminal PVS and prolong survival.
Methods: This is a single-arm, prospective, open-label FDA approved study using bevacizumab and imatinib mesylate to treat progressive multivessel intraluminal PVS. Pts with obstruction of ≥ 2 veins (echocardiographic (Echo) mean gradient ≥ 4 mmHg) were included after aggressive surgical or catheter based relief of obstruction. All but 3 pts had ≥ 1 PVS surgery prior to initiation. Pts with CHD received imatinib mesylate only, those without CHD or who progressed on study also received bevacizumab. Follow-up included lung scan and Echo q 4-8 weeks (wks); CT scan or angiography q 24 wks. We report initial (31 of 44 enrolled pts) who have reached 48 wks or study endpoint.
Results: Among 31 pts, 17 were treated for 48 wks; 3 transplanted; 11 discontinued drug < 48 wks. Mean age at diagnosis was 4 mos; drug initiation 9 mos. Two had isolated disease, 16 CHD, 3 lung disease, 10 both. Twenty-four pts received imatinib mesylate only; 7 both drugs. Median number of pulmonary veins involved was 4 (range 2-5); 12 pts had ≥ 1 atretic vessel at initiation. Pts received mean of 85% planned doses of drug. At 48 wks, 26/31 (84%) were alive, 2 post-transplant. Eight of 31 (26%) stabilized, 6/31 (19%) did not require any subsequent pulmonary vein intervention.
Conclusions: Multi-modal treatment including aggressive surgical and catheter based intervention and targeted inhibition of myofibroblast proliferation resulted in a 48 wk survival of 84% among pts with multivessel intraluminal PVS. These results suggest that targeted inhibition may play an important role in managing aggressive pulmonary vein disease.
Author Disclosures: K. Western: None. M. Kieran: Research Grant; Modest; Pre-clinical Trial Novartis, Pre-Clinical Trial Roche/Genetech. Consultant/Advisory Board; Modest; On the Novartis board for therapeutic development of novel therapeutic agents for pediatric brain tumors. C. Baird: None. C. Ireland: None. S.D. Colan: None. K. Gauvreau: None. A.C. Marshall: None. L. Sena: None. K.J. Jenkins: Research Grant; Significant; Our group receives research support from Johns Hopkins for a study involving NuMed and Medtronic products.. Other Research Support; Modest; Our research group may receive free drug from Lantheus for a separate study.. Other Research Support; Significant; Novartis has provided free drug for this study.
- © 2014 by American Heart Association, Inc.