Subclinical Leaflet Thrombosis in Surgical and Transcatheter - PowerPoint PPT Presentation

Subclinical Leaflet Thrombosis in Surgical and Transcatheter Bioprosthetic Aortic Valves Results from RESOLVE and SAVORY registries Raj R. Makkar, MD On Behalf of RESOLVE and SAVORY Investigators

Disclosures Consulting fee and research grants from Edwards LifeSciences, St. Jude Medical and Medtronic

4D-CT Angiogram of Bioprosthetic Aortic Valve Hypoattenuating opacity Reduced leaflet motion

Volume rendered CT images of bioprosthetic valves Normal leaflets Thickened leaflets with thrombus Systole Systole Diastole Diastole Makkar R. et al. NEJM 2015

Background • Subclinical leaflet thrombosis, presenting as reduced leaflet motion on CT, associated with hypoattenuating leaflet thickening – Is reported in 10-15% of patients after TAVR. – Is noted in both transcatheter and surgical bioprosthetic aortic valves. – Is less common in patients on therapeutic anticoagulation with warfarin and resolves with initiation of warfarin. • However, there are no data on differences between surgical and transcatheter aortic valves, impact of NOACs on the prevention and treatment of this finding, and limited data on valve hemodynamics and clinical outcomes. Makkar R. et al. NEJM 2015; Pache G. et al. EHJ 2015; Yanagisawa R. et al. JACC: Cardiovascular Interventions 2016; Hansson NC. et al. JACC 2016; Ruile P. et al. Clin Res Cardiol 2017

Study Objectives To study subclinical leaflet thrombosis of bioprosthetic aortic valves in terms of • Prevalence in a large heterogenous cohort of patients • Differences in TAVR and SAVR • Impact of novel-oral anticoagulants (NOACs) • Impact on valve hemodynamics • Impact on clinical outcomes

Study design 657 patients underwent CTs in 274 patients underwent CTs in the RESOLVE registry the SAVORY registry Cedars-Sinai Medical Center, Los Angeles Rigshospitalet, Copenhagen 931 patients undergoing CTs 890 patients with interpretable CTs were included in the analysis RESOLVE registry: 626 patients SAVORY registry: 264 patients

Valve types and timing of CT Time from TAVR to CT vs. SAVR to CT: p<0.0001 890 patients with interpretable CTs Median time from AVR to CT 83 days (IQR 32-281 days) 752 transcatheter valves 138 surgical valves Median time from TAVR to CT Median time from SAVR to CT 58 days (IQR 32 – 236 days) 162 days (IQR 79 – 417 days)

CT Imaging and Evaluation • All CTs were analyzed at Cedars-Sinai Heart Institute in a blinded manner by a dedicated CT core laboratory. • Hypoattenuated leaflet thickening of the valve leaflets was assessed using 2D (axial cross-section assessment) and 3D-VR (volume rendered) imaging. Leaflet motion was assessed using four- dimensional volume-rendered imaging. • Quantification of reduced leaflet motion was based on analysis of a volume-rendered en-face image of the aortic valve prosthesis at maximal leaflet opening. • Reduced leaflet motion was defined as the presence of at least 50% restriction of leaflet motion.

Reduced leaflet motion was defined as the presence of at least 50% restriction of leaflet motion A Normal leaflet motion Reduced leaflet motion Hypoattenuating opacities

Study methodology • All echocardiograms were analyzed in a blinded manner. • Data on the antiplatelet and antithrombotic therapy were collected on all clinic visits. • Clinical follow-up was obtained in all patients for death, myocardial infarction (MI), stroke and transient ischemic attack (TIA). • All neurologic events, including strokes and TIAs, were adjudicated in a blinded manner by a stroke neurologist.

Reduced leaflet motion in multiple valve types Sapien Evolut R Lotus Portico Centera Symetis Perimount Magna

Prevalence of reduced leaflet motion Transcatheter vs. surgical bioprosthetic aortic valves: p=0.001 Reduced leaflet motion was present in 106 (11.9%) patients Transcatheter valves Surgical valves 13.4% (101 out of 752) 3.6% (5 out of 138)

Baseline characteristics Patients with and without reduced leaflet motion Normal leaflet motion Reduced leaflet motion (N=784) (N=106) p-value Characteristic 78·9 ± 9·0 82·0 ± 8·7 0·0009 Age (years) 437 (55·7%) 64 (60·4%) 0·37 Male sex Medical condition 74 (10·2%) 14 (14·3%) 0·22 Chronic kidney disease 8 (1·2%) 1 (1·0%) >0·99 Hemodialysis 9 (1·4%) 0 (0%) 0·61 Hypercoagulable disorder 679 (86·7%) 88 (83·0%) 0·30 Hypertension 63 (8·1%) 9 (8·5%) 0·88 Prior stroke 36 (4·6%) 6 (5·7%) 0·63 Prior transient ischemic attack 599 (76·6%) 78 (73·6%) 0·49 Hyperlipidemia 193 (24·7%) 22 (20·8%) 0·38 Diabetes 84 (10·8%) 13 (12·5%) 0·60 PCI within 3 months prior to AVR 588 (75·3%) 84 (79·3%) 0·37 Congestive heart failure 47 (6·1%) 3 (2·9%) 0·26 Syncope 233 (29·9%) 17 (16·0%) 0·003 Atrial fibrillation Baseline echocardiogram 57·9 ± 12·6 55·5 ± 13·2 0·07 Ejection fraction (%) 44·2 ± 13·8 44·6 ± 16·1 0·83 Mean aortic valve gradient (mmHg) 74·2 ± 22·1 73·6 ± 26·2 0·79 Peak aortic valve gradient (mmHg) 0·23 ± 0·09 0·22 ± 0·07 0·27 Dimensionless index Data are mean ± SD or n(%) AVR=Aortic valve replacement

Baseline characteristics Patients with surgical and transcatheter aortic valves SAVR TAVR Characteristic (N=138) (N=752) p-value 71·9 ± 8·6 80·7 ± 8·4 Age-year <0·0001 Male sex-no. (%) 88 (63·8%) 413 (54·9%) 0·05 Medical condition - no. (%) Chronic kidney disease 6 (4·8%) 82 (11·7%) 0·02 Hemodialysis 0 (0%) 9 (1·3%) 0·23 Hypercoagulable disorder 0 (0%) 9 (1·4%) 0·61 Hypertension 101 (73·2%) 666 (88·7%) <0·0001 Prior stroke 9 (6·6%) 63 (8·4%) 0·47 Prior transient ischemic attack 3 (2·2%) 39 (5·2%) 0·19 Hyperlipidemia 93 (67·9%) 584 (77·8%) 0·01 Diabetes 28 (20·3%) 187 (24·9%) 0·25 PCI within 3 months prior to AVR 7 (5·2%) 90 (12·0%) 0·02 Congestive heart failure 68 (49·3%) 604 (80·6%) <0·0001 Syncope 2 (1·5%) 48 (6·4%) 0·02 Atrial fibrillation 31 (22·6%) 219 (29·2%) 0·11 Baseline echocardiogram 57·2 ± 11·5 57·7 ± 12·9 Ejection fraction - % 0·30 43·6 ± 14·4 44·4 ± 14·1 Mean aortic valve gradient - mmHg 0·91 72·5 ± 22·3 74·4 ± 22·7 Peak aortic valve gradient - mmHg 0·82 0·26 ± 0·12 0·23 ± 0·08 VTI ratio 0·04 Anticoagulation at the time of discharge 31 (22·5%) 187 (24·9%) 0·54 Anticoagulation at the time of CT 38 (27·5%) 186 (24·7%) 0·49 162·5 days (80 – 417 days) 58 days (32 – 235 days) Timing from AVR to CT <0·0001 0-6 months 74 (53·6%) 520 (69·2%) 6-12 months 26 (18·8%) 84 (11·2%) >12 months 38 (27·5%) 148 (19·7%) AVR=Aortic valve replacement; CT=computed tomogram Data are mean ± standard deviation or median (interquartile range) for continuous variables; N (%) for categorical variables

Baseline characteristics Patients with surgical and transcatheter aortic valves SAVR TAVR Characteristic (N=138) (N=752) p-value 71·9 ± 8·6 80·7 ± 8·4 Age-year <0·0001 Male sex-no. (%) 88 (63·8%) 413 (54·9%) 0·05 Medical condition - no. (%) Chronic kidney disease 6 (4·8%) 82 (11·7%) 0·02 Hemodialysis 0 (0%) 9 (1·3%) 0·23 Hypercoagulable disorder 0 (0%) 9 (1·4%) 0·61 Hypertension 101 (73·2%) 666 (88·7%) <0·0001 Prior stroke 9 (6·6%) 63 (8·4%) 0·47 Prior transient ischemic attack 3 (2·2%) 39 (5·2%) 0·19 Hyperlipidemia 93 (67·9%) 584 (77·8%) 0·01 Diabetes 28 (20·3%) 187 (24·9%) 0·25 PCI within 3 months prior to AVR 7 (5·2%) 90 (12·0%) 0·02 Congestive heart failure 68 (49·3%) 604 (80·6%) <0·0001 Syncope 2 (1·5%) 48 (6·4%) 0·02 Atrial fibrillation 31 (22·6%) 219 (29·2%) 0·11 Baseline echocardiogram 57·2 ± 11·5 57·7 ± 12·9 Ejection fraction - % 0·30 43·6 ± 14·4 44·4 ± 14·1 Mean aortic valve gradient - mmHg 0·91 72·5 ± 22·3 74·4 ± 22·7 Peak aortic valve gradient - mmHg 0·82 0·26 ± 0·12 0·23 ± 0·08 VTI ratio 0·04 Anticoagulation at the time of discharge 31 (22·5%) 187 (24·9%) 0·54 Anticoagulation at the time of CT 38 (27·5%) 186 (24·7%) 0·49 162·5 days (80 – 417 days) 58 days (32 – 235 days) Timing from AVR to CT <0·0001 0-6 months 74 (53·6%) 520 (69·2%) 6-12 months 26 (18·8%) 84 (11·2%) >12 months 38 (27·5%) 148 (19·7%) AVR=Aortic valve replacement; CT=computed tomogram Data are mean ± standard deviation or median (interquartile range) for continuous variables; N (%) for categorical variables

Severity of reduced leaflet motion Surgical vs. transcatheter valves Percentage leaflet Leaflet thickness motion restriction 6 80.0 P=0.004 P=0.0004 71.0% ± 13.8% 5.01 ± 1.81 mm 70.0 5 Percentage leaflet motion restriction 56.9% ± 6.5% 60.0 Leaflet thickness (mm) 4 50.0 3 40.0 30.0 1.85 ± 0.77 mm 2 20.0 1 10.0 0.0 0 SAVR TAVR SAVR TAVR

Number of leaflets affected with reduced leaflet motion • Surgical valves with reduced leaflet motion (n=5) – 1 leaflet involved in 4 patients – 2 leaflets involved in 1 patient • Transcatheter valves with reduced leaflet motion (n=101) – 1 leaflet involved in 70 patients – 2 leaflets involved in 25 patients – 3 leaflets involved in 6 patients