Insights from the Corevalve US Pivotal and SURTAVI trials

Reported from ACC 2022

Background

CoreValve US pivotal and SURTAVI are the two trials that showed superiority of TAVI over surgery in high or extreme risk patients (CoreValve US pivotal) and non-inferiority of TAVI vs. surgery in intermediate risk patients (SURTAVI) up to 5 years. Of note landmark analysis of the SURTAVI trial showed that hemodynamics remained superior with TAVI through 5 years, whereas surgery continued to hold the advantage in terms of paravalvular leak (PVL). Though rates of reintervention and permanent pacemaker implantation within 2 years were higher in the TAVI arm, there were no differences in these outcomes between 2 and 5 years. Importantly, in SURTAVI trial 84% of patients received the 1^st generation Corevalve while others received the Evolut R platform. Of note Evolut Pro and now Evolut Pro + are the contemporary versions of self-expanding Medtronic devices and showed lower rates of PVL compared to Evolut R and Corevalve.

Following guidelines updates, TAVI is a recommended option across all surgical risk levels (ESC guidelines 2021). Therefore regarding low and intermediate risk patients, we expect younger patients with longer life expectancy to be treated with TAVI.

Understanding valve durability and structural valve deterioration (SVD) is key in the management of those patients. 

Data on balloon expanding valves showed that early generations of TAVI devices have higher incidences of SVD, whereas newer generations have similar rates compared to surgery (Pibarot, JACC 2020).

Objective of this analysis

• To analyse the 5 years incidence, outcomes and predictors of hemodynamic SVD in patients undergoing TAVI and surgery from the Corevalve US Pivotal and SURTAVI trials.

Data and study populations

• To compare SVD in TAVI vs. Surgery: Patients from the 2 randomized trials
• To evaluate the predictors of SVD and clinical outcomes: Patients from the 2 randomized trials + addition of patients from CoreValve US extreme risk and Corevalve Continued Access study (CAS).

Definition of SVD (VARC 3- European heart Journal 2021)

Increase in mean gradient >= 10mmHg from discharge echo to last echo AND mean gradient >=20 mmHg on last echo

OR

New onset or increase of intra-prosthetic aortic regurgitation >= moderate.

Statistics

• 5 years incidence of SVD from the 2 randomized trials in surgery and TAVI using Fine-Gray regression and death as competing risk.
• Association of SVD with clinical outcomes (all-cause mortality, cardiovascular mortality and hospitalization for heart failure or aortic valve) using Cox analysis.
• Predictors of SVD using Fine-Gray regression with death as competing risk.

Results: patients

Patients from randomized trials were comparable, while patients from CoreValve US extreme risk and Corevalve continued Access study were older with more comorbidity.

Results: SVD

• Significantly lower rates of SVD with TAVI (2.57%) versus surgery (4.38%) at 5 years (p=0.0095)
• In small annuli (<=23mm) significantly lower rates of SVD with TAVI (1.39%) versus surgery (5.86%) at 5 years (p=0.049)
• In large annuli (>23mm) trends toward lower rates of SVD with TAVI (2.48%) versus surgery (3.96%) at 5 years (p=0.067)
• Stenosis was the more frequent SVD mode compared to regurgitation

Results: clinical outcomes related to SVD

In all patients (surgical, TAVI and combination) SVD was associated with significantly higher risk of all-cause and cardiovascular mortality. In the surgical arm, SVD was associated with non-significant trend for higher risk for hospitalization for aortic disease or HF while in TAVI arm this sur-risk was significantly higher.

Predictors of SVD

In multivariate analysis, patients with SVD were younger, less often male, with less often history of prior percutaneous coronary intervention (PCI) and atrial fibrillation. Conversely, patients with SVD had higher body surface area.

Conclusion

In patients with severe aortic stenosis at intermediate or high surgical risk, the 5 years rate of SVD was lower with TAVI as compared to surgery. The difference was more profound in patients with smaller annuli. Doppler derived SVD was associated with higher all-cause and cardiovascular mortality and a trend in favour of higher risk for hospitalizations for aortic valve disease or worsening heart failure. Predictors of SVD were higher body surface area, while men, older patients and those with previous PCI or atrial fibrillation had lower risk of SVD.

Opening questions

• Up to 10 years the curves may continue to diverge as SVD accelerates with time
• Valve design and Tissue factors (porcine tissue in Corevalve) may explain the differences between TAVI and surgical valve SVD. Hemodynamic are better with supra-annular design and therefore may participate in differences in SVD
• The association between previous PCI and atrial fibrillation and SVD will need to be studied (potential impact of antithrombotic treatments and statin)

Our commentary

The 5-year results from the PARTNER 2 trial, presented at the ACC 2020, showed us that SVD rates were higher in earlier generation of balloon-expandable valves (SAPIEN XT) as compared to surgery, whereas SVD was comparable between TAVR and SAVR when the contemporary SAPIEN 3 valve was implanted. As of yesterday, the interventional community was not aware of the long-term performance of self-expanding valves in terms of long-term SVD, and had TAVR underperformed SAVR, this would have represented a major drawback for any further implementation of TAVR.

That is why the piece of evidence provided by this pooled analysis of the US Pivotal and SURTAVI trials is so important. At 5-year follow-up, SVD rate was significantly lower with TAVR as compared to SAVR. Since SVD has been shown to be associated with all and cardiovascular mortality, this is particularly reassuring in terms of very long-term clinical outcomes after TAVR with self-expanding valves.

These results go along well with favourable long-term outcomes with ViV-TAVR published by Guimaraes LFC et al. in Circulation Cardiovascular intervention in 2018, in which about half of the patients were treated with self-expanding valves, and at a median follow-up of 3 years (up to 7 years) only 3% of the patients exhibited clinically relevant SVD, in line with TAVR for native valves. Also, a propensity-matched analysis published by Tam DY et al in JACC Cardiovascular interventions in 2020 reported that ViV-TAVR was associated with lower early mortality, morbidity, and length of hospital stay and with increased survival compared with redo surgical AVR.

All the pieces of the puzzle seem to converge towards a future in which TAVR will become the treatment of choice even for younger patients, and ViV (or TAVR in TAVR) will be used as a valid treatment option for SVD.

Of course, a number of considerations must be made. First and foremost, we know from surgical studies that bioprostheses degenerate more intensively in younger patients. This is also the case in the present study, in which a younger age was an independent predictor of SVD. Future studies will have to determine what is the age group in which the rate of SVD, although higher than in older patients, is still clinically acceptable.

Also, we still know very little regarding medical therapy in TAVR patients. The fact that atrial fibrillation and previous PCI were protective factors against SVD could imply that anticoagulation, double antiplatelet therapy, or statin therapy might have a positive effect on valve durability.

Finally, this study investigated one type of self-expanding valve, thus results may be difficult to generalize to self-expanding valves with different philosophies. For instance, since hemodynamic parameters seem to be improved with a supra-annular design, it is not known whether the results in terms of SVD would have been similar with annular bioprostheses.

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