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\begin{document}

\title{Left Ventricle Pedunculated Thrombi Risks and Outcomes: A Case Report
and Systematic Review}



\author[1]{Ahmed Ali Ali}%
\author[2]{Eman Elsayed Sakr}%
\affil[1]{National Heart Institute}%
\affil[2]{Mataria Teaching Hospital}%


\vspace{-1em}



  
  \date{May 30, 2024}


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\selectlanguage{english}
\begin{abstract}
We report a case of a 42-year-old male with cardiomyopathy and acute
bilateral femoral artery embolization. Following bilateral femoral
artery embolectomy and fasciotomy, transthoracic echocardiography
revealed a pedunculated highly mobile left ventricle (LV) thrombus.
Surgical removal of the thrombi was not recommended for the procedural
risk; consequently, anticoagulation therapy was recommenced.
Unfortunately for the patient, the bleeding risk impeded the
continuation of anticoagulation, which resulted in an increase in the
thrombus size. The patient shortly developed multiorgan failure and
disseminated intravascular coagulopathy (DIC) and died. Besides this
case, we have systematically reviewed the PubMed and Scopus databases
for all the previously reported pedunculated thrombus/ thrombi cases.%
\end{abstract}%



\sloppy


\textbf{Left Ventricle Pedunculated Thrombi Risks and Outcomes: A Case
Report and Systematic Review}

Ahmed Ali Ali\textsuperscript{1}; Eman Elsayed Sakr\textsuperscript{2}

1 Cardiology Department, National Heart Institute, Giza; Egypt.

2 Cardiology Department, El-Mataria Teaching Hospital, Cairo; Egypt.

Correspondence to Eman Elsayed Sakr

Email: Emansakr94@gmail.com

ORCiD: https://orcid.org/0000-0002-3499-3851

Postal code: 32513

The authors received no funding.

The authors declare no conflict of interest.

Abstract

We report a case of a 42-year-old male with cardiomyopathy and acute
bilateral femoral artery embolization. Following bilateral femoral
artery embolectomy and fasciotomy, transthoracic echocardiography
revealed a pedunculated highly mobile left ventricle (LV) thrombus.
Surgical removal of the thrombi was not recommended for the procedural
risk; consequently, anticoagulation therapy was recommenced.
Unfortunately for the patient, the bleeding risk impeded the
continuation of anticoagulation, which resulted in an increase in the
thrombus size. The patient shortly developed multiorgan failure and
possibly disseminated intravascular coagulopathy (DIC) and died. Besides
this case, we have systematically reviewed the PubMed and Scopus
databases for all the previously reported pedunculated thrombus/ thrombi
cases.

\begin{enumerate}
\tightlist
\item
  Introduction A left ventricle (LV) thrombus is defined as an
  echo-dense mass near an akinetic or hypokinetic ventricular wall that
  is visible in at least two different views . LV thrombi formation
  following acute myocardial infarction (MI) or dilated cardiomyopathy
  (DCM) is predisposed by Virchow's triad (myocardial infarction-induced
  endothelial injury and the subsequent elevation of catecholamine
  levels , inflammation-triggered hypercoagulability, and blood stasis
  due to segmental wall motion ). About 6.3\% of ST segment elevation
  myocardial infarction (STEMI) cases and 19.2\% of anterior STEMI
  patients with LVEF \textless{}50\% are complicated with LV thrombus
  formation within two weeks to three months of the onset of myocardial
  injury. Other risk factors of LV thrombus formation are dilated heart
  failure, hypercoagulable states, nonischemic cardiomyopathy, and
  Takotsubo cardiomyopathy . LV thrombi develop in 1.3\% to 2.2\% of
  patients with acute Takotsubo cardiomyopathy, and they are
  significantly associated with the presence of both apical ballooning
  and high troponin level \textgreater{}10 ng/mL. Pedunculated LV
  thrombi have a higher embolic potential than mural ones depending on
  the extent of protrusion into the left ventricle, mobility, and the
  pedunculated shape. There is no theory explaining the exact mechanism
  or combination of factors that favor the formation of pedunculated
  thrombi. Nonetheless, the literature has reported many mural thrombi
  that partially detached and transformed into pedunculated thrombi
  during follow-up or hospitalization . Herein, we depict a case of
  pedunculated LV thrombus that presented with bilateral acute lower
  limb ischemia and review the literature for similar case presentations
  highlighting the main risks and outcomes.
\item
  Methodology We searched PubMed and Scopus databases using the key
  search terms ``left ventricle OR left ventricular'' AND pedunculated
  AND ``thrombus OR thrombi''. All published reports posing cases of
  pedunculated left ventricular thrombus were included with no
  restriction on the age or year of publication.
\item
  Results
\item
  Presentation of Case
\end{enumerate}

A man in his 40s with a history of diabetes mellitus, hypertension, and
ischemic heart disease with resultant ischemic heart failure presented
with bilateral lower limb pain and loss of motor and sensory activity.
The patient was evaluated in the emergency department and the evaluation
revealed acute bilateral lower limb ischemia that prompted an immediate
surgical intervention.

\emph{Five years before the current presentation,} the patient
reportedly had extensive anterior ST elevation myocardial
infarction\emph{(Figure I) that was treated with streptokinase and
rescue PCI} . Coronary angiography showed 80\% stenosis of the proximal
LAD, for which a drug-eluting stent was deployed. The patient's
transthoracic echocardiography (TTE) showed an ejection fraction (EF) of
45\% with an akinetic apical and mid septum, apical and mid anterior,
and apical inferior segments; normal LV dimensions, and dilated left
atrium. Over four years, the patient had deteriorating heart failure
with EF 30\%, akinetic anteroseptal and mid to apical septal segments, a
restrictive pattern of diastolic function, dilated LV and left atrium,
and mild mitral regurgitation.

\emph{On examination,} the vital parameters recorded systolic blood
pressure of 90 mm hg, heart rate of 89/ min, respiratory rate of 18/
min, and temperature of 36. Laboratory investigations were notable for
leucocytosis (15.300 cells/ microliter), elevated cardiac enzymes (CK-MB
130 U/L; troponin I 71.6-fold the upper normal limit), and an
international normalized ratio (INR) of 1. Other laboratory test results
(hemoglobin, platelets, serum creatinine, serum urea, arterial blood
gas) were normal. Arterial duplex revealed bilaterally damped monophasic
flow across the external iliac artery down to the superficial femoral
artery. Furthermore, there was no detectable flow distally down to the
infra-popliteal arteries. The patient's acute limb ischemia was managed
surgically by bilateral mechanical thrombectomy and fasciotomy.

A TTE was obtained after the operation and elucidated decreased ejection
fraction (20\%, measured by M-mode) with global hypokinesia and a large
pedunculated irregular hypermobile LV thrombus at the LV apex measuring
4.32*2.82 cm (figure II). An electrocardiogram revealed LBBB and
prolonged QT interval.

Cardiothoracic surgery consultation refused the surgery for the
procedural risks; for this, anticoagulation treatment was decided. Soon
after the operation, the patient's condition deteriorated and required
endotracheal intubation. The deterioration entailed circulatory collapse
and multiorgan failure (acute kidney injury, ischemic/ shocked liver,
and disturbed consciousness level). Furthermore, the patient exhibited a
bleeding tendency (hematemesis, melena, and nasal bleeding), which
necessitated discontinuing the anticoagulation; consequently, the
thrombus size increased to measure 4.7*3.9 cm (Figure III). The
laboratory test results were then notable for low hemoglobin (7.4 g/dl),
low platelets (87* 10\textsuperscript{3}/ UL), elevated renal function
test values (serum creatinine 6 mg/dl; urea 267 mg/dl); elevated liver
function test values (AST 1145; ALT 1063), and elevated serum potassium
(6.5 mmol/ dl). The patient eventually died.

Systematic review of literature

Searching PubMed and Scopus databases retrieved 74 and 63 articles,
respectively. After removing duplicates, 90 records were eligible for
the title and abstract screening, which revealed 66 reports to be
eligible for full-text screening. Only cases reporting pedunculated
thrombus/ thrombi at the first assessment for any etiology were
included; records with irretrievable data were excluded; reports of
mural thrombus/ thrombi that transformed into pedunculated thrombi
during the follow-up were also excluded for carrying different risks.
Only 45 cases from 37 papers met our inclusion and exclusion criteria.
The manual search revealed 11 more pertinent cases. Our report was
included in the analysis (figure IV)/ flowchart) to eventually have 57
cases analyzed.

Baseline demographic and clinical data, management, and outcome are
listed in Table I. Overall, the mean age of all the cases was 50.5\selectlanguage{ngerman}±15.6
years, and 66.6\% (38/57) were male. Based on etiology, 41.1\% of cases
(N=24) were attributed to old (N=12) or acute (N=12) myocardial
infarction; 17.5\% (N=10) to cardiomyopathy (non-ischemic dilated
cardiomyopathy, Takotsubo cardiomyopathy, peripartum or idiopathic
cardiomyopathy); and 7\% (N=4) were due to heart failure. Other
etiologies entailed ulcerative colitis (N=2), CoVID-19 infection (N=2),
and coagulopathy (N=6). About 17.5\% (N=10) developed idiopathic LV
thrombi. Combined etiologies were also found .

Twelve (21\%) of the cases had a previous coronary artery disease, 11
(19.2\%) had hypertension, seven (12.2\%) had a smoking history, and
three (5.1\%) had a history of substance abuse (alcohol, anabolic
androgenic steroids, and cocaine). Furthermore, seven (12.2\%) had
diabetes mellitus, five (8.7\%) had coagulopathy (essential
thrombocytopenia, polycythemia vera, and cystic fibrosis for example),
and four (7\%) had hyperlipidemia. Of note, seven cases (12.2\%) had no
identifiable risk factors. The vast majority of LV thrombi were located
at the apex (73.6\%; 42/57) followed by the interventricular septum
(8.7\%; 5/57). However, some cases exhibited more than one thrombus at
two or more sites and three cases did not report the thrombus site
(table II). About 16 (28\%) of cases developed LV thrombus despite
having a normal systolic function on presentation. The etiology of the
LV thrombus was idiopathic in 10/ 16 of these cases, due to a
hypercoagulable state in two cases, and due to ulcerative colitis
inflammatory condition in two cases. It is worth stating that
hypertension was a risk factor in 4/16 (25\%), and the ECG showed
abnormal changes in only 3/16 (18.7\%) of these cases. Thirty-three
patients (57.8\%) developed distal emboli at different sites, yet the
commonest site was the brain (N=14) followed by the arterial system of
the lower limb (N=13). Other sites are displayed in (Table I). The
definitive treatment for most cases was surgical removal (75.4\%; N=43).
Furthermore, three cases responded well to oral anticoagulation with
warfarin. While five cases responded well to heparin infusion, four
cases did not show any improvement, and the management plan was
readjusted to either surgery, tirofiban, recombinant tissue plasminogen
activator (RTPA), or streptokinase.

Discussion

Despite the absence of histopathological confirmation, our patient was
diagnosed with LV thrombus for his associating factors (history of
anterior STEMI with reduced EF) and the current presentation. Surgical
removal is the definitive management of the mobile pedunculated masses
for their high embolization risk . Alternatively, for cases that refuse
or deem to be unfit for surgery, direct oral anticoagulants were
non-inferior to Vit K antagonist (warfarin) in treating LV thrombus .
Based on our review, surgical removal was almost always successful,
whereas oral and intravenous anticoagulation was relatively less
successful (5/12; 41.6\% failure rate). Furthermore, the three cases
that died, entailing our case, were managed using anticoagulation and
did not proceed to surgery. There are no clinical trials assessing the
efficacy of thrombolysis via streptokinase, RTPA, or urokinase.
Nonetheless, thrombolysis carries a high embolic and hemorrhagic risk
despite the potential of successfully dissolving the LV thrombus . The
deterioration of the LVEF in our patient can be explained by the
thrombus given the fact that the LVEF improves or even normalizes after
the removal or dissolution of LV thrombus in some other patients . This
finding has been confirmed earlier where the LAD/ anterior wall
infarctions were significantly associated with contractile dysfunction
at the apex and with decrements in the peak systolic function .
Four-dimensional magnetic resonance imaging (4D MRI) for intracardiac
hemodynamic assessment was tested in anterior MI cases, being the most
reported risk for LV thrombi. It revealed a reduced peak systolic flow
in the mid ventricle and apex and reduced peak diastolic flow in the
apex in anterior acute MI . This explains the occurrence of apical
thrombi in anterior/ LAD MI. However, there is no reported prophylactic
anticoagulation strategy to date. Accordingly, any use of prophylactic
anticoagulation should be tailored on a patient-by-patient basis.
Notably, prophylactic anticoagulation in LV thrombus was a class IIb
recommendation according to the 2013 ACC/AHA STEMI guidelines . Low-dose
anticoagulation with rivaroxaban 2.5 mg BID for 30 days, besides the
dual antiplatelet therapy (DAPT), has been recently tested . The
low-dose rivaroxaban plus DAPT cohort had a lower incidence of LV
thrombus formation as opposed to the DAPT alone cohort (0.7\% and 8.6\%,
respectively; hazard ratio 0.08). On the other hand, anticoagulation has
no role in preventing LV thrombus formation in dilated cardiomyopathy
with sinus rhythm . The Heart Failure Long-Term Antithrombotic Study
(HELAS) trial has also compared the incidence of thromboembolism with
warfarin, aspirin, or placebo in chronic heart failure . There was no
significant difference in the incidence among the three groups. TTE has
been the major diagnostic tool for the literature cases, entailing our
case. Noting the difficulty of diagnosing mural thrombi, and their
potential of transformation into pedicled thrombi, routine assessment of
patients following MI (particularly anterior MI with reduced LVEF) or
cardiomyopathy diagnosis is advised for early diagnosis and management.
Delayed enhancement cardiac magnetic resonance imaging (DE-CMRI) was
revealed to be the most sensitive imaging modality for detecting LV
thrombi and distinguishing them from the normal myocardium . It had a
significantly higher performance than both the standard TTE and
cine-CMRI in detecting LV thrombi . DE-CMRI has a 100\% negative
predictive value and 100\% sensitivity . The absence of vascularity in
the thrombi prevents the late gadolinium enhancement on CMRI increasing
the sensitivity and specificity of such a modality. Nonetheless, DE-CMRI
cannot be afforded for all acute MI patients. So, an algorithm entailing
routine non-contrast echocardiography for stratifying patients based on
apical wall motion score was proposed; the presence of apical wall
motion then warrants performing DE-CMRI. V. Conclusion This report
highlights a pedunculated LV thrombus in a case of toxic cardiomyopathy
with a previous history of anterior acute myocardial infarction.
Multidisciplinary management is a cornerstone in managing similar
complicated cases. Early surgical management of pedunculated LV thrombi
is the management of choice, and it should be considered to avoid the
failure rates of anticoagulation and thrombolytic medications. A clear
diagnostic algorithm should be adopted for early diagnosis and for
avoiding embolic presentations. Similarly, screening algorithms should
also be developed for patients with non-ischemic cardiomyopathies and
those liable for LV thrombosis with normal LV function, inflammatory
bowel disease, and hypercoagulable states for example. Furthermore,
large clinical trials on the efficacy of prophylactic anticoagulation
following acute MI, specifically anterior/ LAD MI are needed. References\selectlanguage{english}
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