Percutaneous pulmonary valve replacement after different duration of free pulmonary regurgitation in a porcine model: effects on the right ventricle Mads Ersboll a, Niels Vejlstrup a, Jens Christian Nilsson a, Jesper Kjaergaard a, Wendy Norman b, Theis Lange d, Andrew Taylor b,c, Philipp Bonhoeffer b,c and Lars Sondergaard a a The Heart Centre, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark b Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom c UCL Institute of Child Health, London, United Kingdom d Department of Biostatistics, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark
Presenter Disclosure Information Mads Ersboell, MD Percutaneous pulmonary valve replacement after different duration of free pulmonary regurgitation in a porcine model: effects on the right ventricle DISCLOSURE INFORMATION: No Disclosures
Background Free Pulmonary regurgitation after corrected Tetralogy of Fallot Progressive RV dilatation Excercise intolerance Arrythmias Pulmonary valve replacement Need for multiple procedures Longevity of conduit Child growth Irreversible RV failure
Study aims Effects of free PR on RV volumes over time Right ventricular end diastolic volume index (ml/m 2 ) Right ventricular end systolic volume index (ml/m 2 ) Remodeling of RV after pulmonary valve replacement Predictors of response to pulmonary valve replacement
Study design 44 farm pigs (8-9 weeks old, 13.5 kg) Divided into 4 groups (A,B,C,D) A,B & C: Free PR from bare metal stent in Pulmonary annulus (CP, Numed) D: Control with no intervention
Free PR by insertion of CP stent
Study design Group A,B & C Percutaneous pulmonary valve replacement after 1,2 & 3 months respectively (Melody, Medtronic) RV adaptation 1 month after pulmonary valve replacement
Implantation of Melody stent valve
Study design MRI & RV cath in group A,B & C Before PR Before pulmonary valve replacement After 1 month with valve MRI & RV cath in group D Baseline as well as 1,2,3 & 4 months
MRI Control after 3 months Free PR after 3 months
MRI 3 months free PR prior to PPVR Same animal 1 month after PPVR
Study design Group A Free PR PPVR Group B Free PR PPVR Group C Free PR PPVR Control 0 1 2 3 4
Effects of pulmonary regurgitation RVEDV index 350 13.3 kg 24.6 kg 42.6 kg 60.8 kg 82.6 kg 300 RVEDV index (ml/m2) 250 200 150 100 Sham operated control 3 month free PR 2 month free PR 1 month free PR 50 0 1 2 3 4 Months
Effects of pulmonary regurgitation 140 RVESV index 120 RVESV index (ml/m2) 100 80 60 40 Sham operated control 3 month free PR 2 month free PR 1 month free PR 20 0 1 2 3 4 Months
Effects of pulmonary valve replacement 350 RVEDV index 300 RVEDV index (ml/m2) 250 200 150 Sham operated control 3 month free PR 2 month free PR 1 month free PR 100 50 0 1 2 3 4 Months
Effects of pulmonary valve replacement RVESV index 140 120 RVESV index (ml/m2) 100 80 60 40 Sham operated control 3 month free PR 2 month free PR 1 month free PR 20 0 1 2 3 4 Months
Results RV volumes increased significantly during PR Response defined as decrease in RV volumes was found in all animals after 1 month treatment with PPVR. Significant variation in magnitude of response to treatment was observed.
Results Predictor of RV volumes 1 month after pulmonary valve replacement RV volume increase from baseline to valve replacement (p<0.001, R 2 =0.80) No predictive value Duration of PR Pulmonary regurgitant fraction RV & PA pressure Porcine Brain Natriuretic Peptide Degree of tricuspid regurgitation
Probability of full recovery Probability of full recovery and RV dilatation during free PR Full RV recovery after pulmonary valve replacement was defined as: RV EDVi and RV ESVi upper 2SD value of control animals. Full recovery was modeled as a function of increase in RV volume index during PR 350 RV ESV index 300 250 200 150 100 RV EDV index 50 0 1 2 3 4 Change in RV volume index from baseline to PPVR (ml/m 2 )
Limitations Short duration of PR compared to ToF 1. Rapid growth to adolescent/adult size RV non-restrictive at induction of PR No VSD patch or scarring of RVOT 2. Compliant RV amplify the response to volume overloading 3. Pure model of PR without fibrosis * Smith J, et al, Myocardial hypertrophy after pulmonary regurgitation and valve implantation in pigs, Int J Cardiol(2011), doi:10.1016/j.ijcard.2011.02.022
Conclusion The model produces free PR with severe RV dilatation and absence of fibrosis. RV dilatation was succesfully reverted with PPVR in all animals. RV dilatation during PR was the only predictor of RV volume after pulmonary valve replacement. Full recovery of RV volume was only dependent on RV dilatation during PR. No other markers of pending RV failure could be identified.
Perspective Confirmation of retrospective data indicating point of no return of RV dilatation* RV dilatation without concomitant fibrosis is predictive in itself of full recovery after pulmonary valve replacement. Serial monitoring of RV function with MRI after ToF repair with trans annular patch. Oosterhof T, et al. Circulation. 2007 jul;116(5):545-51. Vliegen HW, et al. Circulation. 2002 sep;106(13):1703-7. Therrien J, et al. Am J Cardiol. 2005 mar 15;95(6):779-82.
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No difference in amount of fibrosis Control animal 3 months free PR Smith J, et al, Myocardial hypertrophy after pulmonary regurgitation and valve implantation in pigs, Int J Cardiol(2011), doi:10.1016/j.ijcard.2011.02.022