JACC: CARDIOVASCULAR IMAGING

VOL. 10, NO. 1, 2017

2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

PUBLISHED BY ELSEVIER

ISSN 1936-878X/$36.00
http://dx.doi.org/10.1016/j.jcmg.2016.11.009

Leaet Thrombosis in Surgically

Explanted or Post-Mortem TAVR Valves
Fernanda M. Mangione, MD,a Tannas Jatene, MD,a Alexandra Gonalves, MD, PHD, MMSC,a Gregory A. Fishbein, MD,b
Richard N. Mitchell, MD, PHD,b Marc P. Pelletier, MD,c Tsuyoshi Kaneko, MD,c Pinak B. Shah, MD,a
Charles B. Nyman, MBBCH,d Douglas Shook, MD,d Ron Blankstein, MD,a Robert F. Padera, MD, PHD,b
Deepak L. Bhatt, MD, MPHa
LEAFLET THROMBOSIS IS CURRENTLY ONE OF THE GREATEST CONCERNS RELATED TO TRANSCATHETER

aortic valve replacement (TAVR). Symptomatic valve thrombosis is a rare occurrence, but reduced leaet
motion, diagnosed by computed tomography, seems to be a more common nding (1).
We screened our pathology registries for patients with a prior TAVR who underwent a post-mortem examination or who had a TAVR device surgically explanted in an attempt to understand better the causes of TAVR
failure. Of 13 valves studied, we found 4 cases of leaet thrombosis diagnosed only on pathological examination
(Figures 1 to 4, Online Videos 1, 2, and 3). Two of the patients had a valve-in-valve TAVR (Figures 1 and 3), and in 3
cases, there was incomplete expansion or asymmetry of the valve (Figures 1, 2, and 4). None of the patients were
on anticoagulation. There were also 2 cases of endocarditis, 1 coronary obstruction, and 2 cases of paravalvular
leak. The other 4 patients had no substantial valve ndings.
TAVR valve thrombosis is underdiagnosed, and the mechanisms for its development might be associated
with underexpansion and asymmetry of the valve. Valve-in-valve TAVR may be associated with these features
more often and might be a risk factor for leaet thrombosis.

From the aBrigham and Womens Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts; bBrigham
and Womens Hospital Department of Pathology and Harvard Medical School, Boston, Massachusetts; cBrigham and Womens
Hospital Department of Surgery and Harvard Medical School, Boston, Massachusetts; and dBrigham and Womens Hospital
Department of Anesthesiology and Harvard Medical School, Boston, Massachusetts. Dr. Gonalves has received funds from the
Portuguese Foundation for Science and Technology, Grant HMSP-ICS/007/2012. Dr. Pelletier is a consultant for St. Jude
Medical. Dr. Kaneko is a consultant for Edwards Lifesciences. Dr. Shah is a proctor for Edwards Lifesciences; and a course
director for Edwards Lifesciences and St. Jude Medical. Dr. Nyman has received educational honoraria and holds stock in
Edwards Lifesciences. Dr. Shook has received education honoraria from Edwards Lifesciences, Sorin Group, and Boston
Scientic; and is a consultant for Edwards Lifesciences. Dr. Padera is a pathology consultant for Medtronic, Direct Flow, and
Boston Scientic. Dr. Bhatt is on the advisory boards of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and
Regado Biosciences; is on the board of directors of Boston VA Research Institute and the Society of Cardiovascular Patient
Care; chairs the American Heart Association Quality Oversight Committee; is on data monitoring committees for Duke Clinical
Research Institute, Harvard Clinical Research Institute (including for his role as DMC Chair of the PORTICO trial), Mayo Clinic,
and the Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior
Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical
Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee),
HMP Communications (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest
Editor; associate editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief
Medical Editor, Cardiology Todays Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), and WebMD
(CME steering committees); has other relationships with Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering
Committee (Vice-Chair), and VA CART Research and Publications Committee (Chair); has received research funding from
Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pzer, Roche,
Sano Aventis, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A
Companion to Braunwalds Heart Disease); has been a site coinvestigator for Biotronik, Boston Scientic, and St. Jude Medical;
is a trustee of the American College of Cardiology; and has performed unfunded research for FlowCo, PLx Pharma, and
Takeda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Manuscript received August 23, 2016; revised manuscript received November 14, 2016, accepted November 16, 2016.

Mangione et al.

JACC: CARDIOVASCULAR IMAGING, VOL. 10, NO. 1, 2017

JANUARY 2017:825

TAVR Leaet Thrombosis

F I G U R E 1 Undiagnosed Valve-in-Valve Leaet Thrombosis Related to Incomplete TAVR Expansion Leading to Surgical Aortic Valve Replacement

An 82-year-old man, who previously underwent surgical aortic valve replacement, developed very rapid stenosis of the bioprosthetic valve 2 years after
the surgery. He underwent a successful TAVR, but after 6 months, his new valve also developed stenosis. Transesophageal echocardiography showed the
transcatheter valve with diffuse thickening inside the bioprosthetic surgical valve. No thrombus was seen (Online Videos 1 and 2). The mean pressure
gradient was 56 mm Hg (A). The patient had been chronically treated with aspirin and clopidogrel. He underwent a successful surgical aortic valve
replacement. Post-explantation assessment of the valves showed a very calcied surgical valve (B, arrow). The Edwards Sapien valve (Edwards Lifesciences, Irvine, California) had a low position of implantation (B) and incomplete expansion causing deformation of the leaets (C). There was thrombus
in the outow of all 3 cusps resulting in restriction of motion and subsequent stenosis (C, arrows). Microscopic image showing the Sapien cusp with a
thrombus (D, arrow). TAVR transcatheter aortic valve replacement.

FIGURE 2

Early Leaet Thrombosis Related to Asymmetry of the TAVR

An 88-year-old man underwent TAVR complicated by aortic regurgitation and

refractory hypotension, that resolved after additional balloon expansion. One
week after, the patient developed acute peripheral artery occlusion and underwent left supercial femoral artery thrombectomy with stent placement. He was
receiving dual antiplatelet therapy, and heparin was added. Immediately postprocedure, his hematocrit signicantly dropped, and after 3 hours, he had a
sudden cardiac arrest. Autopsy ndings showed the Edwards Sapien device in the
aortic position with a distorted oval shape, likely related to the severe atherosclerosis and calcication of the aorta. Due to this conguration, the left and
right coronary leaets were unable to coapt fully, resulting in an abnormal ow
that may have predisposed to the formation of an organizing thrombus behind
the right coronary leaet (arrow). The autopsy also revealed signs of signicant
upper gastrointestinal hemorrhage. TAVR transcatheter aortic valve
replacement.

83

84

Mangione et al.

JACC: CARDIOVASCULAR IMAGING, VOL. 10, NO. 1, 2017

TAVR Leaet Thrombosis

JANUARY 2017:825

F I G U R E 3 Valve-in-Valve Leaet Thrombosis Associated With Severe Cardiac Amyloidosis

An 83-year-old man underwent transfemoral TAVR. A few days after the procedure, he developed symptoms of heart failure, and transesophageal echocardiography
revealed moderate-to-severe aortic regurgitation (A and B). An Edwards Sapien valve-in-valve was placed, and a smaller leak was closed successfully using an
Amplatzer Vascular Plug (C, black arrow). One month later, he underwent subtotal colectomy due to a colitis, and his warfarin was discontinued. He was discharged with
aspirin, and approximately 30 days after that, he developed severe respiratory failure and expired. Autopsy ndings revealed the transcatheter valve without any
evident structural or mechanical defects. Thrombus with subacute organization was found in both atrial appendages and ventricles, attributed to stasis due to poor
cardiac function in the setting of severe amyloid-induced restrictive physiology. A thrombus with minimal organization was also present on 2 of the cusps of the TAVR
contributing to functional aortic stenosis (C to F, red arrows). TAVR transcatheter aortic valve replacement.

Mangione et al.

JACC: CARDIOVASCULAR IMAGING, VOL. 10, NO. 1, 2017

JANUARY 2017:825

TAVR Leaet Thrombosis

F I G U R E 4 Early Leaet Thrombosis Related to Asymmetry and Underexpansion of the TAVR

A 75-year-old woman underwent transfemoral TAVR immediately complicated by a left bundle branch block. The patient was discharged 3 days later on aspirin and
clopidogrel. One day after discharge, she was admitted with chest pressure, pulmonary edema, and new-onset atrial brillation. Transthoracic echocardiography
showed diffuse thickening of the transcatheter valve (A, arrow) (Online Video 3), but no increase in the mean pressure gradient (10 mm Hg [B]) and severe decrease in
left ventricle ejection fraction (from 50% to 30%) with new anterior and septal segmental dysfunction. Her hospital course was complicated by hemodynamic
instability, and she expired after 24 h of hospitalization. Autopsy ndings showed low implantation of the Edwards Sapien 3 valve, impinging on the basal surface of
the myocardium and compressing the AV node (C). The valve showed asymmetry due to incomplete expansion and presence of thrombus on the valve leaets (D and
E). There was multifocal acute ischemic damage to cardiomyocytes. AV atrioventricular; TAVR transcatheter aortic valve replacement.

REPRINT REQUESTS AND CORRESPONDENCE: Dr. Deepak L. Bhatt, Brigham and Womens Hospital Heart &

Vascular Center and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115. E-mail:
dlbhattmd@post.harvard.edu.

REFERENCE
1. Makkar RR, Fontana G, Jilaihawi H, et al. Possible
subclinical leaet thrombosis in bioprosthetic aortic
valves. N Engl J Med 2015;373:201524.

KEY WORDS aortic stenosis, autopsy,

pathology, TAVR, thrombosis

A PPE NDI X For supplemental videos,

please see the online version of this article.

85