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?