gender disparities among patients undergoing transcatheter aortic valve replacement michael a....
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GENDER DISPARITIES AMONG PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT
Michael A. Gaglia, Jr.; Michael J. Lipinski; Rebecca Torguson; Jiaxiang Gai; Itsik Ben-Dor; Lowell F. Satler; Augusto D. Pichard; Ron Waksman
Medstar Heart and Vascular Institute
Washington, DC
Background
• Studies regarding mortality after SAVR are conflicting, although high-risk female patients appear to have worse outcomes than male
• In PARTNER, Williams et al reported women had lower rates of late mortality with TAVR vs. SAVR– Driven by females with transfemoral access
• Recent meta-analysis by O’Connor et al of 11,310 TAVR patients:– Long-term mortality: female lower (no diff at 30d)– Stroke, major bleed, vascular complications: female higher
Heart 2010;96:539; J Thorac Cardiovasc Surg 2014;147:1529; JACC 2014;63:1522; JACC 2015;66:221
Hypothesis
• Women undergoing TAVR, compared to men, will have lower mortality rates at 1 year
• Women undergoing TAVR, compared to men, will have higher rates of major bleeding and vascular complications
Methods – Cohort Selection
• Database of 752 patients undergoing TAVR for severe, symptomatic AS at Washington Hospital Center (study and commercial patients)
• Includes both balloon-expandable and self-expanding valves
• In-hospital, 30 day and 1 year outcomes stratified by gender, access route, and valve type– Outcomes defined according to VARC 2
Methods - Statistics
• Categorical variables compared using Fisher’s exact test
• Continuous variables compared using Student t test
• Survival curves used Kaplan-Meier estimates and compared using log-rank test
• Multivariable Cox regression for mortality at 1 year
Results – Baseline CharacteristicsFemale (n=382) Male (n=372) p value
Caucasian 81.3% 88.0% 0.02
African American 15.6% 9.0% 0.009
Age 83.5 ± 7.7 82.4 ± 7.7 0.049
Hypertension 92.4% 95.4% 0.09
Diabetes mellitus 31.1% 35.4% 0.22
COPD 35.0% 34.1% 0.80
Current smoking 0.3% 3.9% 0.002
Atrial fib/flutter 36.5% 46.0% 0.01
GFR <60 or dialysis 41.8% 53.0% 0.003
Hx CABG 19.1% 48.3% <0.001
Hx PCI 24.9% 36.9% <0.001
Hx MI 13.9% 23.8% <0.001
PVD 28.4% 41.9% <0.001
Results – Baseline MeasurementsFemale (n=382) Male (n=372) p value
STS score 9.8 ± 4.6 8.0 ± 4.4 <0.001
MLD Right 6.7 ± 1.1 7.6 ± 1.3 <0.001
MLD Left 6.7 ± 1.1 7.6 ± 1.4 <0.001
AVA (cm2) 0.63 ± 0.13 0.70 ± 0.13 <0.001
LVEF ≤40% 16.2% 30.1% <0.001
Mean AV gradient 50.1 ± 13.3 44.9 ± 11.5 <0.001
LVEDD (cm) 4.20 ± 0.68 4.70 ± 0.75 <0.001
LV septal thickness 1.30 ± 0.22 1.35 ± 0.25 0.006
LVPW 1.20 ± 0.20 1.25 ± 0.19 0.002
PASP 45.6 ± 16.6 44.2 ± 15.5 0.31
Results – Procedural CharacteristicsFemale (n=382) Male (n=372) p value
Transfemoral 76.2% 82.0% 0.052
Transapical 19.3% 16.4% 0.30
Commercial 34.3% 36.9% 0.46
Sapien 46.9% 43.7% 0.38
Sapien XT 21.6% 17.1% 0.12
CoreValve 18.9% 27.2% 0.007
23 mm valve 67.0% 15.7% <0.001
26 mm 20.1% 50.9% <0.001
29 mm 8.6% 19.7% <0.001
31 mm 1.1% 12.5% <0.001
Post moderate or worse AR 2.4% 3.9% 0.29
Post mean AV gradient 12.6 ± 5.3 10.7 ± 4.4 <0.001
Post AVA (cm2) 1.43 ± 0.30 1.71 ± 0.55 0.29
30 days: F 9.4% vs. M 5.4%, p=0.035
1 year: F 20.6% vs. M 21.5%, p=0.87
Mortality up to 1 Year post-TAVR: Female vs. Male
Mortality at 1 year post-TAVR by Gender and Access
Overall p for trend=0.027
Mortality at 1 year post-TAVR by Gender and Access
Overall p for trend=0.027
Women TF vs. Women TA: p=0.056
Mortality at 1 year post-TAVR by Gender and Access
Overall p for trend=0.027
p=
Women TF vs. Men TF: p=0.87
Mortality at 1 year post-TAVR by Gender and Access
Overall p for trend=0.027
p=
Women TF vs. Men TF: p=0.87
Women TA vs. Men TA: p=0.94
Men TF vs. Men TA: p=0.07
Mortality at 1 Year by Gender and Valve Type
Mortality at 1 Year by Gender and Valve Type
Women SE vs. Women BE: p=0.62
Mortality at 1 Year by Gender and Valve Type
Women SE vs. Men SE: p=0.84
Mortality at 1 Year by Gender and Valve Type
Women BE vs. Men BE: p=0.23
Men SE vs. Men BE: p=0.03
In-Hospital Outcomes (VARC 2)
All-cau
se m
ortality
CV morta
lity
Stroke
Life-th
reatening b
leed
Majo
r vasc
ular
Minor v
ascular
Stage
3 AKI0.0%
2.0%
4.0%
6.0%
8.0%
10.0%
12.0%
14.0%
16.0%
18.0%
20.0%
8.4%7.6%
4.0%
10.1%
12.3%
16.9%
2.3%
4.3%3.5% 4.1%
5.4%
8.1%
13.7%
1.4%
FemaleMale
p=0.02 p=0.01
p=0.02
p=0.06
Results – In-Hospital Bleeding and Vascular Complications
Female (n=383) Male (n=372) p value
Hb drop >12 8.1% 7.6% 0.83
Any transfusion 43.7% 29.0% <0.001
AV fistula 0.6% 0.3% 1.0
Access site hematoma 15.3% 13.8% 0.58
Pseudoaneurysm 5.2% 3.5% 0.30
Retroperitoneal bleed 5.5% 2.6% 0.06
Lower extremity ischemia 2.2% 1.3% 0.40
Arterial perforation 6.2% 3.5% 0.12
Arterial dissection 8.0% 2.9% 0.004
Surgical repair access site 8.4% 3.6% 0.01
Endovascular repair access site
12.1% 6.5% 0.02
Cardiac tamponade 1.8% 0.3% 0.07
Results: Multivariable Logistic Regression for All-Cause Mortality at 30 Days
Hazard Ratio 95% CI p valueFemale 1.56 0.89-2.75 0.12Age (per 5 years) 1.06 0.88-1.29 0.53Chronic Renal Insufficiency 1.58 0.91-2.76 0.11Transfemoral Access 0.35 0.20-0.60 <0.0001
Results: Multivariable Cox Regression for All-Cause Mortality at 1 Year
Hazard Ratio 95% CI p valueFemale 0.85 0.59-1.22 0.37Transfemoral access 0.63 0.42-0.95 0.027Chronic renal insufficiency 1.49 1.04-2.14 0.028Age (per 5 years) 1.00 0.89-1.12 0.97Peripheral vascular disease 1.03 0.71-1.50 0.89History of myocardial infarction
1.22 0.80-1.88 0.36
LVEF ≤40% 1.16 0.78-1.74 0.45Self-expanding valve 0.90 0.55-1.45 0.66
Mortality at 1 Year Among Patients with Stroke
Alive Dead TotalFemale 11 4 15Male 6 9 15
p value for Fisher’s exact test = 0.14
Limitations
• No data regarding FEV1 (to assess severity of pulmonary disease) – known to be associated with mortality after TAVR
• Multivariable adjustment limited by number of events
• Retrospective registry with highly variable patient population, and evolving technology– Both very early and recent experience with TAVR
Conclusion
• Females have higher rates of short term (30 day) all-cause mortality after TAVR– Mortality rates at 1 year, however, are similar to males– Trend for higher mortality after stroke in male patients may
contribute• Females at higher risk for life-threatening bleeding and
most vascular complications • Unlike some previous studies, females did not have
increased risk for stroke• Significant trend for improved survival with
transfemoral access, regardless of gender
Early Hazard of TAVR in Women
• Linked to higher rates of bleeding and vascular complications– Does hazard exist with smaller devices and improved
strategies for mitigating access complications?• Lower overall rates of major bleeding and vascular
complications in meta-analysis by O’Connor et al– Rates of mortality at 30 days no different between men
and women, better for women at 1 year• Is long-term survival trend in women driven by
lower burden of comorbidities, or TAVR itself?
Discussion• Women overall have longer life expectancy than men
– Does this account for similar survival despite higher complication rate?
• Women have higher STS scores despite having less comorbidities than men– Is STS score really valid in women undergoing TAVR?
• Women with AS have higher levels of interstitial fibrosis than men with AS, and more rapid reversal of LVH post AVR– Does LV respond differently to TAVR in women vs. men?
• If women have worse outcomes than men post SAVR, should TAVR be preferred in women?