ACC 2019 Day 1: PARTNER 3, Evolut Low Risk Trial and Apple Heart Study

Reported from the ACC 2019 (ACC.19) Scientific Sessions in New Orleans.

Coming to New Orleans most of us set our session planner expecting a slow start to the meeting. The LBCTs relevant to the interventional community were scheduled for Sunday, March 17, 2019. To my surprise, the debate around #TAVI/TAVR started early with predictions and implications. Many felt if the results were positive for intermediate risk patients, likely there would be at least an equipoise in low-risk individuals. Much of the discussion boiled down to patient age and durability of TAVR.

However, soon after the Reuters and New York Times released the conclusions of PARTNER 3 TRIAL, the New England Journal of Medicine published the entire trial unleashing disappointment and discussion one day before the trial was due to be presented at ACC19. Davide Capodanno’s comments represent those of many: “A moment of reflection on how horrible it is when you look forward to highly anticipated LBTs presentations…results are leaked one day in advance.”

Let’s examine these results closer for both the balloon expandable & self-expanding technologies:

PARTNER 3

This trial enrolled 1,328 low-risk individuals with an STS score <4% (mean 1.9%). The average age was 73 years of whom 30% only were women. This was a randomized trial comparing outcomes of surgically implanted bioprosthetic valves (SAVR) and those of the transcatheter Edwards Sapien S3 valve (TAVR). Unlike PARTNER 2, the valve implanted was the Sapien S3 version and not the XT delivered exclusively via the transfemoral approach. The usual exclusion criteria were implemented including bicuspid aortic valve. The primary outcome was a composite of all-cause mortality, strokes, and rehospitalizations at 1 year. This endpoint occurred in 8.5% of the TAVR arm and 15.1% of the SAVR arm.

The secondary endpoints of atrial fibrillation and length of stay were lower in TAVR. Bleeding was lower in the SAVR arm. There was no difference in the rate of pacemakers or moderate to severe paravalvular regurgitation. There was, however, a higher rate of mild paravalvular regurgitation and valve thrombosis in the TAVR arm. The clinical significance of this secondary endpoint is difficult to determine primarily because of the short follow up (1 year). In addition, these are echocardiographic findings with no correlating symptoms. Finally, longer follow-up is necessary to determine progression of the regurgitation.

Will PARTNER 3 and EVOLUT Low Risk change your practice?

Also read a review of the PARTNER 3 results by Elad Asher and Salvatore Brugaletta.

#PARTNER3 LBT presentation #ACC19. TAVR associated with a staggering 46% reduction of the primary endpoint of Death,stroke&rehosp and a 66% reduction of death or stroke. @PCRonline@sbrugaletta@djc795@hect2701@DFCapodanno@Ortega_Paz@mmamas1973@mirvatalasnag@MartyMleonpic.twitter.com/0h9JGxYnhy

— Francesco Costa (@Costa_F_8) March 17, 2019

Evolut Low Risk Trial

Evolut Low Risk Trial enrolled just over 1,400 patients (700 in each arm) with a mean STS of 1.9% and an average age of 74 years. Women constituted approximately 33% of the total. The Valves used were primarily Evolut R and PRO versions. Less than 4% were CoreValve. The primary endpoint was disabling stroke or death at 24 months. The results demonstrated that the rate of death with TAVR using a Self-Expanding system was non-inferior to SAVR (4.5% at 24 months). It is noteworthy that the rate of disabling stroke was 1.1% and 3.5% with TAVR and SAVR respectively at 24 months. The secondary endpoint of atrial fibrillation was higher in the SAVR group.

The rate of permanent pacemaker was higher with TAVR (17.4% compared to 6.1%) as well as paravalvular regurgitation. However, the mean gradient was lower in the TAVR group. Of note, the 30-day results for TAVR are impressive and clearly superior to SAVR with respect to death and stroke (0.8% compared to 2.6%).

With two trials determining short term safety, I believe it remains premature to extend TAVR to the low-risk group without a longer follow-up period. Unanswered questions include durability of the valve especially in a young patient, progression of the paravalvular regurgitation, those with concomitant coronary disease, and bicuspid aortic valves.

What else created buzz on day one?

Apple Heart Study

The study is a prospective single arm design with the purpose of evaluating the ability of a smartwatch notification algorithm to identify atrial fibrillation. It was also designed to guide subsequent clinical evaluation. Anyone with a self-reported diagnosis of atrial fibrillation or flutter or on anticoagulation was excluded. The trial was performed exclusively using an application downloaded on an iPhone. This included the consent and initiation/follow-up of the study. Participants wore a patch ECG monitor. Pulse was detected via photoplethysmography.

The primary outcomes were the following:

• AF or atrial flutter for more than 30 seconds detected on subsequent ECG monitoring for those who received a notification.
• Simultaneous ambulatory ECG monitoring indicating AF or atrial flutter during intervals when the tachogram is positive.

Over 400,000 participants were recruited. At 8 months, 0.5% of the total had an irregular rhythm notification. The rate of notifications was only 0.16% in those younger than 40 years. 34% with a positive notification, had atrial fibrillation. The notification of an irregular pulse was concordant with the patch in 84% of the participants. 57% of the participants with a notification were able to reach a clinician with the result.
There are several limitations to this design. Its observational and hence cannot be used as a tool for stroke management. There was no simultaneous ECG data with the initial notification, short ambulatory ECG may not capture true AF burden, and dependence on participants to initiate study may exclude those who are not savvy with the technology or have low adherence. Sensitivity is only 47%. Specificity is 95% for the studied population and may not be reflective of a higher risk group. The design inherently creates bias in the ECG patch cohort compared to the notification cohort.

Overall, two issues remain with regards to this study:

• The clinical decision making that follows this screening process is yet to be defined particularly in asymptomatic individuals.
• What this trial has done, however, is illustrate to researchers the tremendous potential for revolutionizing how research is conducted starting with the enrollment and through the follow-up.

#ACC19 AppleHeart study@PCRonline@EuroInterventiopic.twitter.com/oBE2m2h4zd

— mirvat (مرفت عبدالله الأصنج) (@mirvatalasnag) March 16, 2019

Read more about Late Breaking trials presented at the ACC.19