Is TAVR the treatment of choice for high risk diabetic patients with aortic stenosis? Insights from the FRANCE2 Registry E Van Belle, E Teiger, F Juthier, A Vincentelli, B Iung, H Eltchaninoff, J Fajadet, M Laskar, C Banfi, P Leprince, A Leguerrier, A Prat, and, M Gilard. for the FRANCE2 Registry Investigators
Background Diabetes mellitus (DM) is involved in aortic stenosis development and is associated with qualitative changes in valvular tissue (inflammation, metalloproteinase, ) DM has a negative impact on immediate and long term outcome after surgical aortic replacement. While DM is not part of the Euroscore, it has been integrated to the STS score. The impact of DM on post-transcatheter aortic valve replacement (TAVR) outcome is unknown.
N=348
Objective To compare the outcome of diabetic vs nondiabetic patients, including the primary outcome of the combined occurrence of death and/or stroke in the overall FRANCE2 Registry population and according to device technology and delivery route
External database monitoring and quality control was perfroemd in each patients Methods 3195 consecutive patients were prospectivelly enrolled between January 2010 and October 2011 in 34 French centers and included in the FRANCE 2 Registry. Participation of all french centers and inclusion of all patients in France 2 was mandatory by «legal» request. TAVI was performed with a Balloon- or a Self-expandable device TTE was performed at baseline in all patients and before discharge in 2769/3025 (92%) of the eligible population. Peri-valvular AR was graded as none/trivial(=0), mild(=1), moderate(=2), moderate-to-severe(=3), or severe(=4). An AR grade 2 was considered significant.
Methods Clinical Follow-up was obtained in all patients at 302 days ±164 days. All adverse events were assessed according to the VARC classification The primary outcome was the combined rate of death and/or stroke at 1 year. Secondary outcomes were: - Post-procedural AR grade2 by TTE; - Device success, - Mortality rates at 30-days and 1-year, - Stroke rates at 30-days and 1-year. - Other VARC periprocedural complications including vascular complication, bleeding, myocardial infarction, and acute kidney injury were also reported.
Baseline Clinical Characteristics Diabetics N=797 (25.8%) Non-diabetics N=2298 (74.2%) P Age, years 81.0±6.7 83.3±7.3 <0.0001 Male 55.3% 49.6% <0.005 BMI, kg/m 2 27.9±5.2 25.4±4.7 <0.0001 Hypertension 77.5% 63.7% 0.01 Coronary artery disease, 56.7% 43.0% <0.0001 History of MI 21.6% 14.0% <0.0001 Periperal arterial disease 26.8% 17.9% <0.0001 Renal insuffiencecy 12.2% 8.3% 0.08 Logistique Euroscore 20.4[12.4-30.3] 19.9[12.4-30.0] 0.98 STS Score 11.6[6.5-22.3] 9.6[5.3-20.0] 0.001
Baseline Echocardiography Characteristics Diabetics N=797 (25.8%) Non-diabetics N=2298 (74.2%) P Annulus diameter (pre-procedural TTE) 22.2±2.1 22.1±2.2 0.22 LVEF, % 52.1±13.7 53.5±14.3 0.01 Aortic valve area (cm2) 0.68±0.18 0.67±0.18 0.12 Mean Aortic gradient (mmhg) 45.6±14.9 48.9±17.0 <0.0001 AR grade 2,n 14.0% 17.8% 0.01 MR grade 2, n 18.3% 21.5% 0.06
Procedural Characteristics
Combined rate of Death and/or Stroke according to diabetic status 25 Death or stroke, % 20 15 10 5 Unadj.P=0.04 adj. HR=0.62[0.43-0.91], p=0.01 Non-diabetics Diabetics 0 0 50 100 150 200 250 300 350 Days
Post-procedural Perivalvular regurgitation grade 2 according to diabetic status % 25 23.5 P=0.008 Diabetics Non-diabetics 20 15 10 5 P=0.001 17.1 11.8 P=0.02 15.4 14 10.1 18.9 13.9 P=0.04 11.1 6.1 0 Overall N=3195 N=2138 (66.9%) N=1057 (33.1%) Femoral N=2382 (74.5%) Balloon- Expand. Self- Expand. non- Femoral N=813 (25.4%)
Predictors of Perivalvular Aortic Regurgitation Grade 2 : A multivariate analysis Male Gender Diabetes Mellitus MR at baseline AR at baseline Aortic Annulus mm, TTE) Atrial Fibrillation Self Expendable Device Femoral Approach Prosthesis mm increase) 0 1 2 3 4 5 Odds ratio p 0.0001 0.02 0.02 0.04 0.01 0.11 0.0001 0.002 0.01 Other parameters in the model are : Age, individual euroscore parameters, BMI, LV ejection fraction, Atrial Fibrillation.
Device sucess according to diabetic status % 100 90 80 P=0.005 86.9 82.7 P=0.02 88.8 P=0.04 85 84.5 78.6 P=0.01 93.2 P=0.01 87.4 85.2 80.9 Diabetics Non-diabetics 70 Overall N=3195 N=2138 (66.9%) N=1057 (33.1%) Femoral N=2382 (74.5%) Balloon- Expand. Self- Expand. non- Femoral N=813 (25.4%)
Stroke and Mortality rate according to diabetic status Stroke Mortality Stroke, % 5 4 3 2 P=0.03 Mortality, % 25 20 15 10 P=0.14 1 adj. HR=0.27[0.08-0.86], p=0.01 5 adj. HR=0.84[0.68-0.1.13], p=0.10 0 0 0 50 100 150 200 250 300 350 Days Non-diabetics 0 50 100 150 200 250 300 350 Days Diabetics
Combined rate of Death and/or Stroke Stratified by delivery approach P for interaction=0.02 30 Death or stroke, % 25 20 15 10 5 Diabetics vs non-diabetics/non-femoral, P=0.001 Diabetics vs non-diabetics/femoral, P=0.67 Non-diabetics/non-femoral Diabetics/non-femoral Non-diabetics/femoral Diabetics/femoral 0 0 50 100 150 200 250 300 350 Days
Stroke and Mortality rate stratifed by delivery approach Stroke Mortality P for interaction=0.04 P for interaction=0.04 10 8 Diabetics vs non-diabetics/non-femoral, P=0.006 Diabetics vs non-diabetics/femoral, P=0.32 30 25 Stroke, % 6 4 Mortality, % 20 15 10 2 0 5 0 Diabetics vs non-diabetics/non-femoral, P=0.02 Diabetics vs non-diabetics/femoral, P=0.72 0 50 100 150 200 250 300 350 0 50 100 150 200 250 300 350 Days Non-diabetics/non-femoral Diabetics/non-femoral Non-diabetics/femoral Diabetics/femoral Days
Summary Despite a higher risk profile, diabetic patients with AS undergoing TAVR have a favorable outcome compared to non-diabetic patients. When treated through a femoral approach, diabetics have the similar good outcome than non-diabetic patients. When treated through a non-femoral approach, diabetics do not experience the extra-risk usually associated with this approach.
Perspective While the trans-femoral approach must remain the standard approach for non-diabetic patients, a non-femoral approach is a very reasonable alternative in the diabetic population. Considering the high risk associated with the presence of DM in patients with AS undergoing conventional surgical valve replacement, our data suggest that TAVR, including through a non-femoral route, could become the treatment of choice for high-risk diabetic patients with AS. It demonstrates also that DM should not be counted as a negative variable in preprocedural TAVR scores.