1. Costs of Periprocedural Complications in Patients Treated with Transcatheter Aortic Valve Replacement:
Results from The PARTNER Trial
Suzanne V. Arnold, MD
on behalf of The PARTNER Trial Investigators and The PARTNER Publications Office
ACC | Washington D.C. | March 30, 2014

2. Disclosures: None

3. Background
Transcatheter aortic valve replacement (TAVR) improves survival and quality of life compared with nonsurgical therapy in patients with severe aortic stenosis
TAVR is associated with high in-hospital and long- term costs
A formal economic evaluation demonstrated that the benefits of TAVR were achieved at an acceptable incremental cost to society
Reynolds et al. Circulation. 2012;125:

4. Background
With any emerging technology, complications should decrease with greater operator and site experience as well as improved devices
Since complications were not rare in PARTNER, the costs of treating complications could have substantially impacted the overall cost of TAVR

5. Study Goal
To estimate the incremental cost of specific peri-procedural complications of TAVR
To estimate the contribution of peri- procedural complications to the overall cost of TAVR in The PARTNER Trial
This will allow us better understand the potential economic benefits of avoiding such complications in the future and their impact on the cost-effectiveness of this rapidly evolving procedure.

6. Methods Patient Population
As-treated TAVR patients in PARTNER I Cohorts A & B with billing data available
Costs
U.S. health care perspective
2010 U.S. dollars
Combination of hospital billing data and resource- based accounting methods

7. Peri-Procedural Complications
Death
CVA
major and minor
Myocardial infarction
Vascular complication
Renal insufficiency
serum creatinine >3 mg/dL
Renal failure
need for dialysis
Major bleeding
Arrhythmia
high-degree AV block, atrial fibrillation or flutter, or ventricular tachycardia
New permanent pacemaker
Repeat TAVR
Surgical AVR
Adjudicated by a centralized, clinical events committee

8. Methods: Statistical Analysis
Incremental costs and LOS of each complication, independent of demographic and clinical factors and other complications
Series of models to identify patient predictors of complications, patient predictors of costs in patients without complications, potential interactions
Saturated model included all complications
Reduced model identified only complications significantly associated with costs (or LOS)
Considered both log-transformed and untransformed costs

9. Results Patient Population
Enrolled in PARTNER
N=1057
Mean age: 84 years
47% female
Mean AVA: 0.66 cm2
95% NYHA III-IV
TAVR Patients
N=519
–113 patients without
billing data
Billing Data Available
N=406
No Complications
N=225
≥1 Complication
N=181 (45%)
1 Complication
N=79 (20%)
2 Complications
N=36 (9%)
≥ 3 Complications
N=66 (16%)

10. Results: Table 1 Characteristic Complication n=181
No Complication n=225
p-value
Age (years)
84.4 ± 6.5
82.8 ± 7.4
0.022
Female
54%
41%
0.008
Prior bypass surgery
32%
47%
0.002
Peripheral vascular disease
38%
0.057
6MWT attempted
53%
63%
0.050
6MWT distance (m)
140 ± 89
158 ± 116
0.216
Aortic valve area (cm2)
0.64 ± 0.18
0.67 ± 0.21
0.074
STS predicted mortality (%)
11.9 ± 4.5
11.4 ± 3.8
0.262
Cohort B
39%
22%
<0.001
Transfemoral approach
79%
80%
0.786

11. Complication Rates
With Major Bleeding
7.1%
0.5%

12. Unadjusted Costs of Complications
Mean cost for the initial hospitalization was $78,282 ± 40,790 ($47,322 excluding the valve) and the mean LOS was 10.3 days
Patients with a complication had higher costs and longer LOS compared with those who did not
Unadjusted incremental cost of $33,196
Unadjusted incremental LOS of 6.6 days

13. Adjusted Incremental Costs
*Adjusted for age, sex, prior bypass surgery, peripheral vascular disease, diabetes, and STS mortality risk score; R2=0.41

14. Adjusted Incremental Costs
*Adjusted for age, sex, prior bypass surgery, peripheral vascular disease, diabetes, and STS mortality risk score; R2=0.41

15. Adjusted Incremental LOS
*Adjusted for age, sex, prior bypass surgery, peripheral vascular disease, diabetes, and STS mortality risk score; R2=0.29

16. Attributable Costs and LOS
Attributable costs and LOS were calculated by multiplying the independent cost of the event from the regression model coefficients by its frequency in the study population
This allows us to better understand the contribution of specific complications to the overall cost and LOS for the patients in PARTNER

17. Incremental Cost of Complication Frequency of Complication in PARTNER
Attributable Costs
Complication
Incremental Cost of Complication
Frequency of Complication in PARTNER
Attributable Cost
Death
$42,008
4.9%
$2,069
Major stroke
$16,272
3.2%
$521
Major bleeding
$32,869
9.9%
$3,238
Renal failure
$68,051
2.2%
$1,509
Arrhythmia
$16,067
$514
Repeat TAVR
$119,905
0.5%
$591
Surgical AVR
$26,070
1.7%
$449
Total cost of complications 
$8,892

18. Incremental LOS of Complication Frequency of Complication in PARTNER
Attributable LOS
Complication
Incremental LOS of Complication
Frequency of Complication in PARTNER
Attributable LOS
Death
4.3
4.9%
0.2
Major vascular + major bleed
4.0
7.1%
0.3
Major vascular - major bleed
-1.4
4.4%
-0.1
Minor vascular + major bleed
2.6
0.5%
0.0
Minor vascular - major bleed
1.7
7.4%
0.1
Major bleeding - vascular
17.4
2.2%
0.4
Renal failure
18.3
Arrhythmia
16.3%
0.7
Total LOS impact of complications 
2.0 days

19. Costs and LOS of TAVR

20. Limitations
Cost data were available for only 406 patients, which limits our ability to obtain precise estimates of the costs associated with rare complications
These will need to be examined in larger datasets
All patients were enrolled in a clinical trial, representing the earliest experience with TAVR at most sites
Should have primarily affected rates of complications and the costs of uncomplicated hospitalizations
Complications were defined by PARTNER Trial protocol, prior to VARC publication

21. Conclusions
Peri-procedural complications were common and associated with substantial costs and increased LOS both on a per event basis (i.e., incremental cost or LOS) as well as on a per hospitalization basis (i.e., attributable cost or LOS)
Bleeding, death, and post-procedure renal failure led to the greatest increases in overall costs
Interventions targeted to reduce these complications would be expected to yield the greatest benefit in terms of improving the cost-effectiveness of TAVR

22. Conclusions
Complications accounted for nearly 20% of non- implant related hospital costs
Since ~80% of hospitalization costs were not related to complications, reductions in the cost of uncomplicated TAVR will also be necessary to optimize the value of the technology
Either by reducing post-procedure LOS or through a “minimalist approach” to the implant procedure

23. Thank you

24. ADDITIONAL SLIDES

25. Complications Definitions
Stroke (major)
Focal neurologic deficit ≥24 hours or focal neurologic deficit lasting <24 hours with imaging findings of acute infarction or hemorrhage Modified Rankin Scale of ≥2 at ≥30 days after
Stroke (minor)
Acute stroke with Modified Rankin Scale of 0-1 at ≥30 days
Renal insufficiency
serum creatinine >3 mg/dL
Renal failure
need for renal replacement therapy
Arrhythmia
High-degree AV block, atrial fibrillation or flutter, or ventricular tachycardia
Permanent pacemaker
Arrhythmia requiring permanent pacemaker placement
Repeat TAVR
Implantation of new percutaneous aortic valve
Surgical AVR
Conversion to surgical aortic valve replacement

26. Complications Definitions
Major bleeding
Clear site of bleeding that met any one of the following: (1) caused death, (2) prolonged hospitalization ≥24 hours due to treatment of bleeding, (3) required pericardiocentesis or procedure for repair or hemostasis, (4) caused permanent disability (e.g. blindness, paralysis, hearing loss), (5) required transfusion of >3 units of blood within 24 hr period
Myocardial infarction
(1) acute MI demonstrated by autopsy, (2) emergent PCI or thrombolytics for acute STEMI, (3) peri-procedural MI (≤7 days post index procedure): new pathologic Q waves in ≥2 leads with elevation of CK-MB; or documented signs or symptoms of ischemia or new ischemic changes on ECG and CK-MB elevation >10xULN. (4) non-procedural MI (>7 days): new pathologic Q waves in ≥2 contiguous leads with elevation of CK, CK-MB or troponin and signs or symptoms of myocardial ischemia; or elevation of CK >2xULN with elevation of CK-MB or troponin and signs or symptoms of myocardial ischemia.

27. Complications Definitions
Vascular complication (major)
(1) any thoracic aortic dissection, (2) access site or access-related vascular injury (dissection, stenosis, perforation, rupture, arterio-venous fistula, pseudoaneurysm, hematoma, irreversible nerve injury, or compartment syndrome) leading to either death, need for significant blood transfusions (> 3 units), unplanned percutaneous or surgical intervention, or irreversible end-organ damage (e.g., hypogastric artery occlusion causing visceral ischemia or spinal artery injury causing neurologic impairment), (3) distal embolization (non-cerebral) from a vascular source requiring surgery or resulting in amputation or irreversible end-organ damage, or (4) left ventricular perforation.
Vascular (minor)
Vascular complication not meeting major criteria

28. Methods: Statistical Analysis
Unadjusted hospital cost and LOS for all patients and for the complication categories are presented as mean ± standard deviation
Unadjusted incremental costs and LOS of each complication:
Mean cost or LOS of patients with complication – mean cost or LOS of patients without complication

29. Adjusted Incremental Costs
Step 1: Identify patient factors associated with complications
Logistic regression model with backwards selection p<0.1 with “any complication” as the dependent variable
Step 2: Identify patient factors associated with costs in patients without complications
GLM model with log-link with backward selection p<0.1 with costs as the dependent variable

30. Adjusted Incremental Costs
Step 3: Independent predictors of costs reduced
Linear regression model including age, sex, all covariates identified in Steps 1 & 2 all forced in
Peri-procedural complications were included with backwards selection p<0.1
Interactions between vascular complications and bleeding and between arrhythmias and pacemaker were considered and retained if p<0.1
Step 4: Independent predictors of costs saturated
Repeat Step 3 with all peri-procedural complications

31. Unadjusted Incremental Costs

32. Adjusted Incremental LOS
*Adjusted for age, sex, prior bypass surgery, peripheral vascular disease, diabetes, and STS mortality risk score