When Does Baseline Left Ventricular Function Influence Survival Post Transcatheter Aortic Valve Implantation? —The CoreValve Australia New Zealand Study — Sanjeevan Pasupati, Waikato Hospital, Hamilton, New Zealand Anthony Walton, Epworth and the Alfred Hospitals, Melbourne, Australia Darren Walters, Prince Charles Hospital, Brisbane, Australia Stephen Worthley, Royal Adelaide Hospital, Adelaide, Australia John Ormiston, Mercy Hospital, Auckland, New Zealand Robert Whitbourn, St. Vincent’s Hospital – Melbourne, Australia Gerald Yong, Royal Perth Hospital, Perth, Australia David Muller, St. Vincent’s Hospital – Sydney, Australia Ian T. Meredith, MonashHeart, Monash University Melbourne, Australia UC EE

Potential Conflicts of Interest Speaker's name: Sanjeevan Pasupati  I have the following potential conflicts of interest to report: Consultant: Edwards Lifesciences, Medtronic, Inc., St. Jude Medical Medtronic is the sponsor of the CoreValve Australia-New Zealand Study and provided all statistical analyses and assisted in the graphical display of the data.

Background  The influence of left ventricular (LV) function on the outcomes following transcatheter aortic valve implantation (TAVI) is poorly understood.  Limited data have demonstrated that regardless of baseline LV function, 1- year survival is the same for surgical AV replacement and TAVI. 1  Despite initial favourable outcomes after TAVI, a considerable proportion of patients die within the first 2 years.  We assessed the effect of LV function and the aortic gradient generated by it on the long-term outcomes post TAVI from the ongoing CoreValve Australia and New Zealand Study. 1 Ewe SH, et al. Am Heart J. 160:6: CoreValve Australia-New Zealand Study

Study Design  Prospective, observational study enrolling patients at 10 centres in Australia and New Zealand  Heart Team approach to screen eligible patients  Patients enrolled from August 2008 to October 2012 were included in this analysis  Study enrollment ongoing  100% data monitoring  Independent Clinical Events Committee adjudicated all major adverse events  Assessments at baseline, procedure, discharge and 1, 6, 12 & 24 months * As of June 29, Enrollment ongoing. CoreValve Australia-New Zealand Study

Baseline Characteristics All 4 Groups * P< 0.05 compared to NEF/HG

CoreValve Australia-New Zealand Study 30-day Outcomes All 4 Groups * P< 0.05 compared to NEF/HG Echo parameters were available in 70-75% patients in each group

CoreValve Australia-New Zealand Study 30-day Outcomes All 4 Groups * P< 0.05 compared to NEF/HG

CoreValve Australia-New Zealand Study LV Improvement Baseline Characteristics

Results - The Effect of LV Function  Patients with low EF regardless of baseline AV gradient all died of cardiovascular causes.  Reduced LV function significantly impacted cardiovascular survival at 1 and 2 years.  An absolute increase in EF ≥5% at 1 month occurred in 59% of patients with LEF/LG, and 80% of patients with LEF/HG.  2 years survival (89% vs. 72%) was significantly higher in patients who had a clinically meaningful improvement in LV function 1 month post TAVI.  Prior myocardial infarction was more common in patients with low EF and in patients who showed no improvement or reduction in LV function post TAVI. CoreValve Australia-New Zealand Study

Results – The Effect of AV Gradient  Preserved LV function (EF >50%) and high AV gradient (>40 mmHg) was associated with significantly better all-cause survival (78% vs. 66%, p=0.02) and cardiovascular survival (86% vs. 66%, p=0.001) compared with patients with reduced LV function (EF ≤ 50%) and low AV gradient (≤40 mmHg).  Patients with preserved LV function and low AV gradient (paradoxical low gradient) had significantly better cardiovascular survival than patients with low EF and low gradient at 12 months (p= 0.04), but this was not present at 2 years (p= 0.179).  Patients with paradoxical low gradient and preserved LV function had reduced survival (although not significantly different) from those patients with high AV gradient regardless of LV function. CoreValve Australia-New Zealand Study

 Retrospective  Did not collect dobutamine stress information or pre balloon aortic valvuplasty response, if done prior to TAVI  No core echocardiography laboratory  A multi-variable analysis has not been performed to look at predictors of long-term survival. CoreValve Australia-New Zealand Study Limitations

 Patients with LEF and LG have worse outcomes post TAVI especially if LV function fails to improve post procedure. Balloon aortic valvuloplasty pre TAVI to demonstrate LVEF improvement may be useful to deliver a more cost effective therapy.  Patients with LEF and HG showed sustained improvement in EF with excellent survival and should proceed to TAVI if indicated.  The paradoxical low gradient preserved LV function, severe aortic stenosis patients showed reasonable mid-term benefit and should not be denied TAVI. CoreValve Australia-New Zealand Study Conclusions