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\begin{document}

\title{Anticoagulation for Left Ventricular Thrombi Secondary to COVID -- Is
Three Months Too Long?}



\author[1]{Rimmy Garg}%
\author[1]{Amitoj Sachdeva}%
\author[1]{Juan Del Cid Fratti}%
\author[2]{Samuel Mortoti}%
\affil[1]{University of Illinois Chicago College of Medicine at Peoria}%
\affil[2]{OSF HealthCare System}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\selectlanguage{english}
\begin{abstract}
Length of anticoagulation for thrombotic events related to COVID-19 is
unknown. We present a patient with COVID-19 complicated by a thrombotic
anterior STEMI and multiple left ventricular (LV) thrombi that resolved
after 8 weeks of anticoagulation. We suggest a shorter length of
anticoagulation with COVID-19 related LV thrombus.%
\end{abstract}%



\sloppy


\textbf{INTRODUCTION}

COVID-19 has been associated with venous and arterial thromboembolic
disease likely due to potent local and systemic cytokine production with
subsequent platelet activation, thrombin stimulation, and fibrin
deposition {[}1{]}. Such thromboembolic disease is treated with
anticoagulation but there are no guidelines to direct the types and
duration of oral anticoagulation. We present a case of COVID-associated
acute coronary syndrome (ACS) and left ventricular thrombi with
resolution of the thrombi within 2 months of warfarin initiation.

\textbf{CASE PRESENTATION}

A 62-year-old female with a past medical history of hypertension,
hyperlipidemia, and tobacco use presented with left-sided chest pain
with radiation to the left arm that started the night prior to
admission. She was recently diagnosed with mild COVID-19 infection two
weeks earlier and was treated conservatively as an outpatient. She, nor
her family, has any history of coronary artery disease, heart failure,
or any arrythmias. She was found to be tachycardic but with a regular
rhythm and an otherwise normal physical exam.

Laboratory data was notable for an elevated troponin of 31.2 ng/ml
(reference: \textless{} 0.028 ng/ml) and elevated aspartate
aminotransferase of 177 U/L. Electrolytes and an arterial blood gas
values were within normal range.

ECG demonstrated ST elevations in leads II, III, aVF as well as V3-V5
with ST depression in aVL (Figure 1). With a diagnosis of anterior and
inferior myocardial infarction, patient was taken emergently for a left
heart catheterization (LHC).

LHC showed a thrombotic occlusion of the proximal subsection of the
distal left anterior descending (LAD) coronary artery with evidence of
organized thrombus, judged by the difficulty in passing a wire across
(Figure 2A, Video 1). Multiple balloon dilatations as well as multiple
rounds of aspiration with a penumbra catheter were attempted and
intracoronary eptifibatide was administered with restoration of TIMI 2
flow (Figure 2B, Video 2). Given the presence of organized clot,
decision was to treat medically. The patient otherwise had
non-obstructive disease of the other coronaries. A LHC was repeated 2
days later to see if the thrombus had resolved and stent could be
placed. However, there was still residual thrombus in the distal LAD,
unchanged from prior study (Figure 2C). As patient was chest pain free
and hemodynamically stable, no further intervention was attempted. A
transthoracic echocardiogram (TTE) was performed, demonstrating apical
akinesis with left ventricular (LV) ejection fraction of 39\% by
Simpson's biplane method, as well as multiple large, mobile LV thrombi
with a maximum size of 2cm x 1.5cm (Figure 3A-B, Videos 3-9).

With systolic dysfunction in the setting of STEMI, the patient was
maintained on aspirin, ticagrelor, atorvastatin, metoprolol succinate,
spironolactone, and losartan. She was additionally started on a heparin
drip with bridge to warfarin in setting of multiple large LV thrombi.
Given the size and number of thrombi and associated increased risk of
stroke, cardiac surgery was consulted for potential surgical LV thrombus
evacuation. Surgical intervention was not recommended due to high risk
of complications in the setting of recent ACS, and plan was to continue
medical management.

It was thought that the LAD as well as LV thrombi were secondary to the
patient's recent COVID infection. At time of discharge, aspirin was
discontinued. Ticagrelor was to be continued for a year and warfarin for
at least 3 months based on resolution of thrombi.

Our patient followed up with cardiology and had a repeat TTE 2 months
after hospital discharge. This TTE showed that there was a large apical
aneurysm of the LV but no evidence of any thrombi in the apex (Figure 4,
Videos 10-13). The ejection fraction was still low around 35\%. Warfarin
was continued at this time due to lack of contrast with the last TTE
study, but discontinued 3.5 months later when a repeat TTE with contrast
showed that the LV remained unchanged with no evidence of thrombi
(Figure 5, Videos 14-16).

\textbf{DISCUSSION AND CONCLUSION}

Cardiac manifestations of COVID-19 ACS are due to coronary thrombosis or
acute plaque rupture from systemic inflammation and catecholamine surge
{[}2, 3{]}. For ACS due to plaque rupture, it is recommended that dual
anti-platelet therapy and full-dose anticoagulation be administered in
the acute setting per the American College of Cardiology (ACC)/American
Heart Association (AHA) and the European Society of Cardiology (ESC)
guidelines {[}4{]}. There are currently no specific guidelines on the
anticoagulant used or the duration of anticoagulation in the setting of
coronary thrombosis and/or LV thrombosis related to COVID-19.

As LV thrombus is not an uncommon complication of an acute myocardial
infarction, the 2013 ACC/AHA STEMI guidelines recommend oral
anticoagulation (OAC) use in setting of STEMI with anterior apical
akinesis or dyskinesis to prevent the thrombus formation for 3 months,
aiming for a lower international normalized ratio (INR) of 2.0-2.5
{[}5{]}. The 2017 ESC STEMI guidelines recommend OAC for up to 6 months
with final duration guided by a repeat TTE, risk of bleeding, and need
for concomitant antiplatelet therapy {[}6{]}. The ACTION Study Group
also concluded that anticoagulation for LV thrombus for at least 3
months was associated with a lower risk of major cardiovascular events
or all-cause mortality {[}7{]}.

There have not been any large prospective or direct comparison studies
looking at direct OAC (DOAC) versus warfarin for treatment of LV
thrombus. One metanalysis did show that DOACs appear to be non-inferior
to warfarin without any statistical difference in stroke or bleeding
complications when treating for LV thrombus {[}8{]}.

There have been cases that reported resolution of the LV thrombus in the
setting of COVID-19 infection prior to the 3-month mark. One reported
resolution on a 1-month follow-up TTE while on warfarin {[}9{]} while
another reported resolution at 10 days on low molecular weight heparin
{[}10{]}. Our patient had a large LV thrombus burden that resolved
within 2 months with warfarin use.

As such, a shorter duration of anticoagulation under close supervision
should be considered in patients with COVID-19 related
cardioembolic/thrombotic events, guided by echocardiographic imaging.
Such imaging would require a thorough sweep of the left ventricle in
on-axis and off-axis views so as to not miss any residual thrombi.
Prospective data about proper OAC regimen and duration is still needed.

\textbf{REFERENCES}

\begin{enumerate}
\tightlist
\item
  Ortega-Paz L, Capodanno D, Montalescot G, Angiolillo DJ. Coronavirus
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\item
  Xiong TY, Redwood S, Prendergast B, Chen M. Coronaviruses and the
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\item
  Dominguez-Erquicia P, Dobarro D, Raposeiras-Roub\selectlanguage{ngerman}ín S, Bastos-Fernandez
  G, Iñiguez-Romo A. Multivessel coronary thrombosis in a patient with
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\item
  Bikdeli B, Madhavan M, Jimenez D, et al. COVID-19 and thrombotic or
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\item
  O'Gara ~PT, Kushner ~FG, Ascheim ~DD, ~et al. ~2013 ACCF/AHA Guideline
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\item
  Ibanez ~B, James ~S, Agewall ~S, ~et al; ESC Scientific Document
  Group. ~2017 ESC Guidelines for the management of acute myocardial
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  Cardiology (ESC).~\emph{~Eur Heart J} . 2018;39(2):119-177.
\item
  Lattuca B, Bouziri N, Kerneis, et al. Antithrombotic therapy for
  patients with left ventricular mural thrombus. \emph{J Am Coll
  Cardiol} . 2020;75:1676-1685.
\item
  Dalia, T., Lahan, S., Ranka, S, et al\emph{.} ~Warfarin versus direct
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  https://doi.org/10.1186/s12959-021-00259-w
\item
  Jeon HD, Patel J, Priester T, Moten M. Left ventricular thrombus
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\item
  Sonaglioni A, Albini A, Nicolosi GL, et al. Case report: an unusual
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  by tissue doppler imaging. \emph{Front Cardiovasc Med} . 2021 Jul
  29;8:694542.
\end{enumerate}

\textbf{FIGURES}

\textbf{Figure 1:} EKG demonstrating ST elevations in leads II, III, avF
as well as V3-V5 with ST depression in aVL\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure 2: A-} Thrombotic occlusion of the proximal subsection of
the distal LAD with evidence of organized thrombus. \textbf{B -}Occluded
LAD after PCI with restoration of TIMI 2 flow. \textbf{C -}Persistently
occluded LAD two days after PCI.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

\textbf{Figure 3: A -} TTE without contrast at the off-axis apical 4
chamber view demonstrating multiple LV thrombi. \textbf{B} - TTE with
contrast at the off-axis apical 4 chamber view demonstrating multiple LV
thrombi.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

\textbf{Figure 4:} TTE without contrast at the apical 4 chamber view
shows resolution of LV thrombi.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

\textbf{Figure 5:} TTE with contrast at the apical 4 chamber view shows
resolution of LV thrombi.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image5/image5}

\end{center}
\end{figure}



\textbf{VIDEOS}

\textbf{Video 1} : Thrombotic occlusion of the proximal subsection of
the distal LAD with evidence of organized thrombus

\textbf{Video 2:} Occluded LAD after PCI with restoration of TIMI 2 flow

\textbf{Video 3:} Parasternal short axis view without contrast
demonstrating LV thrombus

\textbf{Video 4 --} Off-axis apical 4 chamber view without contrast
demonstrating multiple large LV thrombi

\textbf{Video 5 --} Apical 2 chamber view without contrast demonstrating
multiple large LV thrombi

\textbf{Video 6 --} Apical 3 chamber view without contrast demonstrating
multiple large LV thrombi

\textbf{Video 7 --} Off-axis apical 4 chamber view with contrast
demonstrating multiple large LV thrombi

\textbf{Video 8 --} Apical 2 chamber view with contrast demonstrating
multiple large LV thrombi

\textbf{Video 9 --} Apical 3 chamber view with contrast demonstrating
multiple large LV thrombi

\textbf{Video 10:} Parasternal short axis view without contrast
demonstrating resolution of LV thrombus

\textbf{Video 11 --} Apical 4 chamber view without contrast
demonstrating resolution of large LV thrombi

\textbf{Video 12 --} Apical 2 chamber view without contrast
demonstrating resolution of large LV thrombi

\textbf{Video 13 --} Apical 3 chamber view without contrast
demonstrating resolution of large LV thrombi

\textbf{Video 14 --} Apical 4 chamber view with contrast demonstrating
resolution of large LV thrombi

\textbf{Video 15 --} Apical 2 chamber view with contrast demonstrating
resolution of large LV thrombi

\textbf{Video 16 --} Apical 3 chamber view with contrast demonstrating
resolution of large LV thrombi\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1-Presenting-EKG/Figure-1-Presenting-EKG}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2---LHC-with-LAD-lesion-pre--and-post-PCI/Figure-2---LHC-with-LAD-lesion-pre--and-post-PCI}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3---TTE-w-and-wo-contrast---LV-thrombi---off-axis-A4C/Figure-3---TTE-w-and-wo-contrast---LV-thrombi---off-axis-A4C}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-4---TTE-noncontrast---Resolution-of-LV-Thrombi/Figure-4---TTE-noncontrast---Resolution-of-LV-Thrombi}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-5---TTE-contrast---Resolution-of-LV-Thrombi/Figure-5---TTE-contrast---Resolution-of-LV-Thrombi}

\end{center}
\end{figure}

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