Original Investigation
Subclinical Leaflet Thrombosis in Transcatheter and Surgical Bioprosthetic Valves: PARTNER 3 Cardiac Computed Tomography Substudy

https://doi.org/10.1016/j.jacc.2020.04.043Get rights and content
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Abstract

Background

Subclinical leaflet thrombosis, characterized by hypoattenuated leaflet thickening (HALT) and reduced leaflet motion observed on 4-dimensional computed tomography (CT), may represent a form of bioprosthetic valve dysfunction.

Objectives

The U.S. Food and Drug Administration mandated CT studies to understand the natural history of this finding, differences between transcatheter and surgical valves, and its association with valve hemodynamics and clinical outcomes.

Methods

The PARTNER 3 (The Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low-Risk Patients With Aortic Stenosis) CT substudy randomized 435 patients with low–surgical-risk aortic stenosis to undergo transcatheter aortic valve replacement (n = 221) or surgery (n = 214). Serial 4-dimensional CTs were performed at 30 days and 1 year and were analyzed independently by a core laboratory.

Results

The incidence of HALT increased from 10% at 30 days to 24% at 1 year. Spontaneous resolution of 30-day HALT occurred in 54% of patients at 1 year, whereas new HALT appeared in 21% of patients at 1 year. HALT was more frequent in transcatheter versus surgical valves at 30 days (13% vs. 5%; p = 0.03), but not at 1 year (28% vs. 20%; p = 0.19). The presence of HALT did not significantly affect aortic valve mean gradients at 30 days or 1 year. Patients with HALT at both 30 days and 1 year, compared with those with no HALT at 30 days and 1 year, had significantly increased aortic valve gradients at 1 year (17.8 ± 2.2 mm Hg vs. 12.7. ± 0.3 mm Hg; p = 0.04).

Conclusions

Subclinical leaflet thrombosis was more frequent in transcatheter compared with surgical valves at 30 days, but not at 1 year. The impact of HALT on thromboembolic complications and structural valve degeneration needs further assessment.

Key Words

hypoattenuated leaflet thickening
leaflet thrombosis
reduced leaflet motion
subclinical leaflet thrombosis

Abbreviations and Acronyms

4D
4-dimensional
AVR
aortic valve replacement
CI
confidence interval
CT
computed tomography
HALT
hypoattenuated leaflet thickening
MI
myocardial infarction
RLM
reduced leaflet motion
RR
risk ratio
TAVR
transcatheter aortic valve replacement
TIA
transient ischemic attacks

Cited by (0)

This work was funded by Edwards Lifesciences. The trial sponsor funded the trial and developed the study protocol in collaboration with the steering committee, with guidance from the U.S. Food and Drug Administration. The sponsor was responsible for site selection, data monitoring, trial management, and statistical analysis. Dr. Makkar has received research grants from Edwards Lifesciences, Abbott, Medtronic, and Boston Scientific; has served as national Principal Investigator for Portico (Abbott) and Acurate (Boston Scientific) U.S. investigation device exemption trials; has received personal proctoring fees from Edwards Lifesciences; and has received travel support from Edwards Lifesciences, Abbott, and Boston Scientific. Dr. Blanke has Computed Tomography Core Laboratory contracts with Edwards Lifesciences, Medtronic, Abbott, and Neovasc (no direct compensation); and has received consulting fees from Edwards Lifesciences, Tendyne/Abbott Laboratories, Circle Cardiovascular Imaging, Neovasc, and Gore. Dr. Leipsic owns stock options in Circle CVI and HeartFlow; has received consulting fees from Circle CVI and HeartFlow; has Computed Tomography Core Laboratory contracts with Edwards Lifesciences, Medtronic, Abbott, and Neovasc (no direct compensation); and has received a research grant from Edwards Lifesciences. Dr. Thourani has received research support from Edwards Lifesciences, Boston Scientific, and JenaValve; and has received consulting fees from Edwards Lifesciences, Boston Scientific, Abbott, Gore Vascular, and JenaValve. Dr. Chakravarty has received consulting fees from Edwards Lifesciences, Abbott, Medtronic, and Boston Scientific. Dr. Brown has received research support to his institution (no direct compensation) from Edwards Lifesciences. Dr. Babaliaros has received research support to his institution (no direct compensation) from Edwards Lifesciences; has received consulting fees from Edwards Lifesciences and Abbott; and holds equity in Trans Mural Systems. Dr. Williams has received research support to his institution from Edwards Lifesciences. Dr. Jilaihawi has received consulting fees from Edwards Lifesciences, St. Jude Medical, Venus Medtech, Medtronic, and Boston Scientific; and has received research support from Medtronic, Abbott Vascular, and Edwards Lifesciences. Dr. Kodali has received research funding to his institution from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott; has received consulting fees from Abbott, Claret Medical, Admedus, and Meril Lifesciences; and has served on the Scientific Advisory Boards of Biotrace Medical, Dura Biotech, and Thubrikar Aortic Valve Inc. Dr. George has received consulting fees from Edwards Lifesciences; and has received institutional research support from Edwards Lifesciences. Dr. Lu is an employee of Edwards Lifesciences. Dr. McCabe has received research funding to his institution from Edwards Lifesciences; and has received consulting fees from Edwards Lifesciences. Dr. Smalling has received consulting fees and research support from St. Jude and Edwards Lifesciences. Dr. Yazdani has served as a proctor for Edwards Lifesciences. Dr. Bhatt has served on the Advisory Boards of Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, and Regado Biosciences; has served on the Boards of Directors of Boston Veterans Affairs Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; has served as the Chair of American Heart Association Quality Oversight Committee; has served on the Data Monitoring Committees of Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards Lifesciences), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo), and Population Health Research Institute; has received honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; REDUAL PCI Clinical Trial Steering Committee funded by Boehringer Ingelheim; AEGIS-II Executive Committee funded by CSL Behring, Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (Clinical Trial Steering Committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Medtelligence/ReachMD (Continuing Medical Education Steering Committees), Population Health Research Institute (for the COMPASS Operations Committee, Publications Committee, Steering Committee, and USA national coleader, funded by Bayer), Slack Publications (Chief Medical Editor, -Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (Continuing Medical Education Steering Committees), Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), and VA CART (U.S. Department of Veterans Affairs Clinical Assessment, Reporting, and Tracking) Research and Publications Committee (Chair); has received research funding from Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Synaptic, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has served as a site coinvestigator for Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), and Svelte; has served as a trustee of American College of Cardiology; and has performed unfunded research for FlowCo, Merck, Novo Nordisk, and Takeda. Dr. Bax has received grants to his institution from Medtronic, Biotronik, Edwards Lifesciences, Abbott Vascular, and Boston Scientific. Dr. Herrmann has received research support to his institution from Edwards Lifesciences, Abbott, Boston Scientific, Bayer, and Medtronic; and has received consulting fees from Edwards Lifesciences and Medtronic. Dr. Mack has received research funding to his institution from Edwards Lifesciences; has received consulting fees from Gore; has served as the Co-Principal Investigator of the PARTNER 3 trial (Edwards Lifesciences, no direct compensation) and as national Co-Principal Investigator of the COAPT trial (Abbott, no direct compensation); and has served as a study Chair for Medtronic. Dr. Leon has received research support to his institution from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott; has served on Advisory Boards for Medtronic, Boston Scientific, Gore, Meril Lifescience, and Abbott; and has served as the Co-Principal Investigator of the PARTNER 3 trial (Edwards Lifesciences, no direct compensation). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. John A. Bittl, MD, served as Guest Editor-in-Chief for this paper.

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