Featured Science and Key Takeaways From TCT 2020 (Part 1)

This is Part 1 of a two-part summary.
Click to access: Part 1 | Part 2

Introduction

This year's Transcatheter Cardiovascular Therapeutics 2020 (TCT 2020), the annual scientific symposium of the Cardiovascular Research Foundation, was virtual. Like the 2020 American College of Cardiology (ACC) Annual Scientific Session Together with World Congress of Cardiology and other virtual cardiovascular meetings occurring during the coronavirus pandemic, TCT 2020 still provided significant evolving science and clinical experience.

This two-part summary of late-breaking clinical trials from TCT 2020 is a slight departure from our usual trial summaries. We offer succinct excerpts from ACC.org meeting coverage to summarize the trials' results, emphasizing shorter expert commentary from members of the ACC Interventional Council. The full ACC.org summaries are referenced and linked for easy access. A new feature is the inclusion of two videos discussing the relevance of trial results. The goal of these videos is to support efficient application of the science to clinical practice.

We look forward to your response to this new format.

Video: What's Practical and Actionable for Interventionalists From TCT 2020 (Part 1)

Drs. George Vetrovec, Mirvat Alasnag, and Peter Block discuss key takeaways for interventionalists from late-breaking clinical trials presented at TCT 2020, including PROSPECT ABSORB (2:05), Disrupt CAD III (5:20), REFLECT II and STS/ACC TVT Registry (8:14), and Bivalirudin vs Heparin in MI Patients (13:10).

Quick Takes

  • The DEFINE-FLOW (Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses) trial showed post-percutaneous coronary intervention (PCI) instantaneous wave-free ratio (iFR) >0.95 was associated with less cardiac death, spontaneous myocardial infarction (MI), or clinically driven target vessel revascularization compared with a post-PCI iFR <0.95, supporting this metric as a marker of optimal PCI results.
  • PROSPECT ABSORB (Providing Regional Observations to Study Predictors of Events in the Coronary Tree II study combined with a randomized, controlled, intervention trial) showed that PCI of angiographically mild lesions with large plaque burden was safe, substantially enlarged 25-month follow-up of minimum lumen area, and was associated with favorable long-term clinical outcomes.
  • REFLECT II (A Randomized Evaluation of the TriGUARD3 Cerebral Embolic Protection Device to Reduce the Impact of Cerebral Embolic Lesions After Transcatheter Aortic Valve Implantation) failed to show that cerebral embolic protection during transcatheter aortic valve replacement (TAVR) was beneficial.
  • The SCOPE I (Acurate neo vs. Sapien 3 Transcatheter Heart Valve System in Patients With Symptomatic Severe Aortic Stenosis) trial showed that the self-expanding ACURATE neo valve (Boston Scientific Corporation; Marlborough, MA) did not meet criteria for noninferiority compared with the balloon-expandable SAPIEN 3 valve (Edwards Lifesciences; Irvine, CA) among patients undergoing transfemoral TAVR.
  • The PARTNER II (Placement of Aortic Transcatheter Valves) trial showed that mortality at five years following valve-in-valve TAVR is comparable with that seen in native TAVR intermediate-risk patients.

Predicting and Treating Future Ischemic Risk (DEFINE-FLOW, PROSPECT ABSORB)
By George W. Vetrovec, MD, MACC
Editorial Team Lead, Invasive Cardiovascular Angiography & Interventions collection on ACC.org
Richmond, VA

ACC.org Excerpts
DEFINE-FLOW showed natural history of abnormal fractional flow reserve (FFR) ≤0.8 but intact coronary flow reserve (CFR) ≥2 is not noninferior to lesions with FFR >0.8/CFR ≥2. Findings from the DEFINE-PCI study found that patients who were highly symptomatic at baseline without residual ischemia by post-PCI instant wave-Free Ratio (iFR) (iFR ≥0.95) tended to have greater improvements in anginal symptoms at one year compared with patients with residual ischemia; a post-PCI iFR ≥0.95 was associated with less cardiac death, spontaneous MI, or clinically driven target vessel revascularization compared with a post-PCI iFR<0.95 (1.8% vs. 5.7% respectively, p=0.04).1

PROSPECT ABSORB showed PCI of proximal non–flow-limiting stenosis with angiographic stenosis <70%, FFR/iFR negative, and plaque burden on IVUS ≥65% with Absorb BVS resulted in a larger MLA on IVUS follow-up, with no difference in clinical endpoints at 24 months. The primary endpoint, MLA on IVUS, for PCI + GDMT vs. GDMT alone, was 6.9 vs. 3.0 mm2 (p < 0.0001); across the entire lesion (including 5 mm margins): 5.2 vs. 2.9 mm2 (p < 0.0001).2

Expert Commentary
The desire to predict (and prevent) late coronary related cardiovascular events based on untreated lesion or post-stent characteristics remains an unfulfilled challenge. The DEFINE-FLOW and PROSPECT ABSORB studies take that hope a bit closer to a reality. The DEFINE-FLOW trial demonstrated that symptom relief and the risk of late events cardiovascular events were significantly reduced when ischemia was eliminated as defined by an iFR of >0.95, supporting the longstanding concept that eliminating ischemia reduces events. Utilizing intravascular ultrasound (IVUS), PROSPECT ABSORB, a therapeutic extension of the diagnostic-only PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) trial demonstrated the potential advantage of stenting non-flow-limiting but high-plaque-burden lesions. Both of these trials are limited in size but form an important basis for definitive trials to confirm the need to reduce residual ischemia and prophylactically treat nonischemic lesions with high plaque burden. These studies continue to support the importance of intravascular coronary imaging techniques to optimize PCI results.

Cerebral Protection During TAVR (REFLECT II)
By Mirvat A. Alasnag, MD
King Fahd Armed Forces Hospital
Jeddah, Saudi Arabia

ACC.org Excerpt
The REFLECT II trial failed to show that cerebral embolic protection during TAVR was beneficial. After enrollment of 179 of the 225 planned randomized patients, the sponsor suspended trial enrollment. The primary safety endpoint at 30 days, all-cause mortality, stroke, life-threatening or disabling bleeding, stage 2/3 acute kidney injury, coronary artery obstruction requiring intervention, major vascular complication, and valve-related dysfunction requiring intervention: 15.9% of the cerebral embolic protection device group. The historical performance goal was 34.4% (p for noninferiority = 0.001). The actual frequency of the composite safety event in the control group was 7.0% (p = 0.11). The primary efficacy score, all-cause mortality or any stroke at 30 days, National Institutes of Health Stroke Scale (NIHSS) worsening from baseline to 2-5 days, freedom from any cerebral ischemic lesions on diffusion-weighted (DW)-MRI at 2-5 days, and total volume of cerebral ischemic lesions on DW-MRI at 2-5 days: -8.58 in the cerebral embolic protection device group vs. 8.08 in the usual care group (p = 0.86).3

Expert Commentary

Although the TriGUARD 3 device (Keystone Heart; Tampa, FL) theoretically permits comprehensive anatomic protection and is easy to deploy, it did not show superiority in the primary efficacy endpoint, which was a hierarchical composite of all-cause mortality or stroke at 30 days. Given the early termination of the study, it remains inconclusive. However, a post hoc analysis of the diffusion-weighted magnetic resonance imaging scans suggested that TriGUARD 3 may reduce larger ischemic lesions. Redefining stroke endpoints to include neurocognitive and imaging criteria may be necessary in future, larger-sized randomized trials. With respect to the primary 30-day safety endpoint, there was a numerically higher incidence of the composite safety endpoint in the TriGUARD 3 arm compared with the control arm. This was primarily driven by TAVR-related vascular and bleeding complications. Overall, the results of REFLECT II are in line with the current body of evidence on the use of embolic protection devices (EPD), including the recently presented STS/ACC TVT Registry, which also demonstrated no difference in in-hospital or 30-day stroke in the primary analysis. Secondary propensity-weighted analysis suggested only a modest reduction in stroke. What is lacking in all the currently available data is defining high-risk populations (the majority of trials excluded those with significant carotid disease, atrial fibrillation, peripheral vascular disease, and advanced kidney disease). Perhaps evaluating the role of embolic protection in such high-risk populations will reveal a benefit. Additionally, the recent SOLVE TAVI (Comparison of Second-Generation Self-Expandable vs. Balloon-Expandable Valves and General vs. Local Anaesthesia in Transcatheter Aortic Valve Implantation) study demonstrated a difference in stroke rates among transcatheter heart valves, showing lower rates in self-expanding valves. Whether this is directly related to the transcatheter heart valve technology itself or operator experience cannot be determined. None of the studies examining embolic protection provided insight on the benefit with respect to transcatheter heart valves or native valve calcification. Furthermore, data on stroke rates and the role of EPD have not been examined in alternative access points (this is an exclusion criterion in the majority of the published trials). All these questions remain unanswered. We know that no stringent protocols govern the use of EPD as demonstrated by the wide variability among centers in the STS/ACC TVT Registry. At this time, there does not appear to be a definitive role for routine EPD in TAVR to reduce neurological events. We are awaiting results of the PROTECTED TAVR (Stroke Protection With Sentinel During Transcatheter Aortic Valve Replacement) trial, which is a large randomized trial with a blinded neurology team evaluation.

TAVR at TCT (SCOPE I, PARTNER 2)
By Wayne B. Batchelor, MD, FACC
Virginia Heart/Inova Heart and Vascular Institute
Falls Church, VA

ACC.org Excerpt
The SCOPE I trial showed that TAVR with the self-expanding Acurate neo valve did not meet criteria for noninferiority compared with the balloon-expandable Sapien 3 valve among patients undergoing transfemoral TAVR. The primary endpoint of death/stroke/bleeding/vascular complications/coronary obstruction/acute kidney injury (AKI)/rehospitalization/repeat intervention/valve dysfunction, for Acurate neo vs. Sapien 3, was 23.7% vs. 16.5% (p = 0.42 for noninferiority, p = 0.016 for superiority).4

PARTNER 2 valve-in-valve TAVR data was analyzed from 365 patients in whom valve implant was   completed. They noted that in survivors, early improvement in functional status and quality of life were maintained for five years. Additionally, rates of heart valve disease and bioprosthetic valve fracture were consistent with those reported for native SAPIEN XT valves in patient with intermediate risk.5

Expert Commentary
The SCOPE I and PARTNER 2 studies provide important insights for the structural heart disease world. From the SCOPE I trial, we learned the following at 1 year:

  • Both the primary composite endpoint and moderate/severe paravalvular leak continued to favor the SAPIEN 3 valve prosthesis over the ACURATE neo valve.
  • Post-TAVR transvalvular gradients remained lower with the ACURATE neo valve.
  • Functional capacity was comparable between groups.

Given these findings, it is tempting to pronounce "advantage SAPIEN 3," but longer-term follow-up (5 years and beyond) will be necessary to determine how these short- to mid-term results and hemodynamics play out over time. This study is valuable because it represents one of several much-needed head-to-head randomized comparisons of contrasting valve technologies. Of note, the ACURATE neo valve is not currently approved by the Food and Drug Administration for commercial use in the Unites States.

The favorable 5-year clinical and functional outcomes observed for the SAPIEN XT prosthesis (Edwards Lifesciences; Irvine, CA) in the PARTNER 2 study also represent additional important structural heart data presented at TCT 2020. Buttressed by sustained improvements in transvalvular gradients and low rates of structural valve degeneration, the favorable long-term clinical results from PARTNER 2 confirm valve-in-valve TAVR as a viable option for treating failing aortic bioprostheses. Still, operators must continue to consider annular size, risk of coronary obstruction, and the future need for additional valve replacements when selecting the optimal aortic valve replacement strategy for any native or valve-in-valve procedure.

References

  1. DEFINE Studies Presented at TCT 2020 Address FFR/CFR and Post-PCI iFR. October 16, 2020 (ACC.org website). Accessed October 19, 2020. Available at https://www.acc.org/latest-in-cardiology/articles/2020/10/15/02/34/fri-1140am-define-flow-tct-2020.
  2. Kumbhani DJ. Providing Regional Observations to Study Predictors of Events in the Coronary Tree II study combined with a randomized, controlled, intervention trial - PROSPECT ABSORB (ACC.org website). October 14, 2020. Accessed October 19, 2020. Available at https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2020/10/13/17/54/PROSPECT-ABSORB.
  3. Bavry AA. A Randomized Evaluation of the TriGUARD3 Cerebral Embolic Protection Device to Reduce the Impact of Cerebral Embolic Lesions After Transcatheter Aortic Valve Implantation - REFLECT II (ACC.org website). October 15, 2020. Accessed October 19, 2020. Available at https://www.acc.org/latest-in-cardiology/clinical-trials/2020/10/14/16/42/reflect-ii.
  4. Kumbhani DJ. Acurate neo vs. Sapien 3 Transcatheter Heart Valve System in Patients With Symptomatic Severe Aortic Stenosis - SCOPE I (ACC.org website). October 17, 2020. Accessed October 19, 2020. Available at https://www.acc.org/latest-in-cardiology/clinical-trials/2019/09/24/23/41/scope-i.
  5. PARTNER 2: Five-Year Outcomes in Patients Undergoing Valve-in-Valve TAVR (ACC.org website). October 14, 2020. Accessed October 19, 2020. Available at https://www.acc.org/latest-in-cardiology/articles/2020/10/15/02/34/sat-115pm-partner-2-tct-2020.

Keywords: TCT20, Transcatheter Cardiovascular Therapeutics, Angina, Stable, Atrial Fibrillation, Cardiac Surgical Procedures, Constriction, Pathologic, Coronary Artery Bypass, Coronary Artery Disease, Drug-Eluting Stents, Fractional Flow Reserve, Myocardial, Ischemia, Myocardial Infarction, Myocardial Revascularization, Percutaneous Coronary Intervention, Quality of Life, Stroke, Thrombosis, Ultrasonography, Natriuretic Peptide, Brain, Kidney Failure, Chronic, Myocardial Revascularization, Transcatheter Cardiovascular Therapeutics, Adrenergic beta-Antagonists, Cardiac Surgical Procedures, Cardiomyopathies, Coronary Artery Bypass, Echocardiography, Geriatrics, Heart-Assist Devices, Heart Failure, Heart Transplantation, Heart Valve Diseases, Mitral Valve Insufficiency, Myocardial Infarction, Myocardial Ischemia, Natriuretic Peptide, Brain, Percutaneous Coronary Intervention, Pulmonary Disease, Chronic Obstructive, Stroke, Stroke Volume, Angina Pectoris, Angina, Stable, Angina, Unstable, Angiography, Coronary Restenosis, Drug-Eluting Stents, Myocardial Infarction, Percutaneous Coronary Intervention, Sirolimus, Stents, Thrombosis, Ultrasonography, Interventional


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