TAVR Studies Tease Out Influences on Clinical Outcome

PARIS, France—New data from the SOURCE XT registry show that a second-generation transcatheter aortic valve replacement (TAVR) device achieves the highest survival yet seen at 30 days with transfemoral access. During the same session at EuroPCR on May 17, 2012, another study explored possible biomarkers to predict mortality after TAVR.

Outcomes Evolve Along with Device

The SOURCE XT registry is designed to measure real-world outcomes in patients implanted with the Sapien XT valve (Edwards Lifesciences; Irvine, CA) from July 2010 to October 2012. Unlike its predecessor SOURCE, which focused on the Sapien valve (Edwards) that became available in 2007, the more recent study involves clinical event committee adjudication and follows the Valve Academic Research Consortium endpoint criteria. Follow-up will continue out to 5 years.

The devices in question also differ, noted investigator Olaf Wendler, MD, PhD, of King's College Hospital/King's Health Partners (London, United Kingdom). Sapien consists of a stainless steel frame and measures 23 or 26 mm, whereas Sapien XT has a cobalt-chromium frame and measures 23, 26, or 29 mm, as well as featuring other design updates.

In SOURCE XT, access route was chosen by the individual centers: 62.6% of procedures were transfemoral, 33.5% transapical, 3.6% transaortic, and 0.3% subclavian. The current analysis focuses on 30-day results with the femoral (n = 1,694) and apical approaches (n = 906). Transapical patients tended to be sicker at baseline, with more comorbidities and worse disease history. Logistic EuroScore was higher in transapical patients than transfemoral patients at 21.8 ± 13.8 and 19.9 ± 12.0, respectively (P= 0.0004); notably, 10.8% of patients treated via transapical access had scores greater than 40 vs. 6.7% of those treated via transfemoral access.

No Surprise, Transapical Patients Fare Worse

Complication rates differed between the 2 access routes, with Sapien-in-Sapien bailout and aborted procedures more commonly seen in transapical patients and cardiac tamponade more frequent in transfemoral patients.

At 30 days, patients treated transapically saw increases in mortality and major bleeding rates, though Dr. Wendler cautioned that this would be expected given their heightened baseline risk (table 1).

Table 1: SOURCE XT: Outcomes at 30 Days

 

 

Transfemoral
(n = 1,694)

Transapical
(n = 906)

All-Cause Mortality

4.3%

9.9%

Any Stroke

2.3%

2.1%

TIA

0.6%

0.7%

MI

0.5%

0.7%

New Pacemaker

8.0%

10.9%

Vascular Complications

7.3%

3.6%

Renal Failure with Temporary Dialysis

1.2%

4.0%

Major Bleeding

5.0%

11.4%

 

But the mortality difference was starkest in patients with logistic EuroScore greater than 40—7.0% with transfemoral and 22.4% with transapical. The latter group “may not benefit from TAVI as much as we would hope,” Dr. Wendler said, noting, “It remains to be seen what effect frailty has on 1-year survival.”

Both access routes, however, saw improvements in ejection fraction at 30 days compared with baseline.  No or trace paravalvular leak was present in 64.8% and 78.7% of the transfemoral and transapical patients, respectively.

Dr. Wendler pointed out that the 4.3% mortality rate in transfemoral patients “is one of the lowest ever reported” for the subgroup in a registry.

Panel member Martin B. Leon, MD, of Columbia University Medical Center (New York, NY), questioned whether the choice of access was patient dependent, with the femoral approach serving as the default, or if it was more operator and site dependent.

Though each site was free to choose, Dr. Wendler replied, there is a shift toward more of the femoral approach in SOURCE XT than in the original SOURCE registry. “The fact that it really has gone up means to me that there are functioning heart teams in place where there is a discussion and decision in favor of transfemoral, because nothing has changed apart from the diameter of the device,” he said.

Sapien XT is improving outcomes for both patient subsets but more clarity will come as the researchers begin to adjust for baseline differences, Dr. Wendler confirmed.

Pilot Study Seeks Prognostic Biomarkers

Researchers led by Petr Kala, MD, PhD, of University Hospital Brno (Brno, Czech Republic), attempted to tease out biomarkers that might predict results of aortic intervention over the first year after treatment.

The researchers prospectively enrolled 42 high-risk elderly patients with symptomatic severe aortic stenosis from 2009 to 2011. Subjects underwent TAVR using the Sapien device (n = 29) or surgical replacement with the Perimount bioprosthesis (n = 13; Edwards). Average age was 82 years, with an average logistic EuroScore of 21.

More than a dozen biomarkers were collected, including those involved in renal function, nitric oxide production, oxidative stress, and metabolism of the extracellular matrix. At 1 year, mortality after TAVR was 13.8%. Several predictors of post-TAVR outcomes were identified (table 2).

Table 2. Predictors of Outcomes After TAVR

 

 

Sensitivity

Specificity

P Value

1-Year Mortality

EuroScore≥ 33.5

 

75.0%

 

96.0%

 

0.015

30-Day VARC Composite

MDA

TIMP-1

MMP-2

Cysteine

 

100%

100%

100%

60.0%

 

95.8%

75.0%

83.3%

95.8%

 

0.004

0.013

0.005

0.030

1-Year VARC Composite

EuroScore II

FRAP

MDA

 

66.7%

76.9%

69.2%

 

74.1%

74.1%

81.5%

 

0.027

0.019

0.007

Abbreviation: VARC, Valve Academic Research Consortium.

 

“Potential contribution of the proposed biomarkers has to be confirmed in large multicenter studies,” and hopefully will also be considered in light of any clinical parameters that are included in a future TAVR risk score, Dr. Kala concluded.

Dr. Leon questioned whether the biomarkers are themselves important or merely markers of underlying risk, but said “this is a very interesting, hypothesis generating analysis.”

Study Details

The 30-day VARC composite was defined as all-cause mortality, major stroke, life-threatening (or disabling) bleeding, acute kidney injury (stage 3), periprocedural MI, major vascular complication, or repeat valve procedure. The 1-year VARC composite was defined as all-cause mortality after 30 days, failure of current aortic stenosis therapy requiring hospitalization, or prosthetic heart dysfunction.

 

Sources:

  1. Wendler O. Thirty-day outcomes from the SOURCE XT TAVI post-approval study. Presented at: EuroPCR. May 17, 2012. Paris, France.
  2. Kala P. Prediction of 1-year prognosis after TAVI and SAVR: Prospective multibiomarker study. Presented at: EuroPCR. May 17, 2012. Paris, France.

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Disclosures
  • Dr. Wendler reports receiving research funding from Edwards Lifesciences and serving as a consultant to Edwards Lifesciences, JenaValve, Medtronic, and St. Jude Medical.
  • Dr. Kala reports no conflicts of interest.

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