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26
Case Study
INTRODUCTION
CASE SUMMARY 1
Infective Endocarditis Associated with Multisystem Inflammatory Syndrome in
Children (MIS-C): Two Case Studies
Tahera Nazrin1, M. Quamrul Hassan2
Sr. Consultant and Coordinator,
Department of Pediatric Cardiology,
Evercare Hospital Dhaka
Sr. Consultant, Department of
Pediatrics &
Address for Correspondence:
Dr. Tahera Nazrin
Sr. Consultant and Coordinator,
Department of Pediatric Cardiology,
Evercare Hospital Dhaka.
tahera.nazrin@evercarebd.com
Infective endocarditis (IE) is the infection of endocardial surface of the heart. IE is the rare
disease with significant complications which require early diagnosis and proper treatment for
reducing morbidity and mortality.IE with vegetation on pulmonary valve, leaflets are uncom-
mon. However, we have diagnosed one case with infective endocarditis associated with Multi-
system Inflammatory Syndrome in Children (MIS-C) which is related with COVID-19.
MIS-C is commonly associated with coronary artery aneurysm (CAA), myocarditis and heart
failure. Our patient had IE and was subsequently affected with MIS-C due to COVID. The
child had vegetation on pulmonary valve with flail pulmonary valve-leaflet with grade II
pulmonary regurgitation and MIS-C related CAA. The second child was previously diagnosed
as infective endocarditis and was treated in other hospital for intravenous antibiotic for four
weeks. However, in our hospital he was diagnosed clinically, by laboratory investigations and
by echocardiography as MIS-C with large vegetation, which was surgically removed, and
biopsy revealed mycobacterium tuberculosis as causative organism.
Infective endocarditis (IE) is an infection of the endo-
cardium, which is caused by various types of microbial
infections. Although this entity is less common, IE can
lead to significant consequences like injury to endocar-
dium, vascular intima or valve, formation of nonbacte-
rial thrombotic endocarditis (NBTE), transient bactere-
mia, adherence of the bacteria or organism to the
NBTE and subsequent rapid multiplication of buried
microorganism within a vegetation. Early diagnosis,
appropriate intervention and management can have a
greater positive impact on reducing IE related morbidi-
ty and mortality. In this case study, we present two
cases with infective endocarditis associated with Multi-
system Inflammatory Syndrome in Children (MIS-C)
which was related to COVID-19 and has been success-
fully managed in this hospital.
1.
2.
A 2 year 3-month-old baby boy weighing 12 kg, height
91 cm, first issue of consanguineous parents was
admitted in EHD with the complaints of fever for 7
days, highest peak of temperature was 104°F associated
with poor feeding and irritability. The baby was at
home and treated with paracetamol. The child had four
episodes of continuous fever (max 104 ˚F) within last
three months with prolonged duration (10 to 15 days)
during this COVID-19 pandemic. His fever was contin-
uous and for this he was admitted in outside hospital
and was empirically treated with antibiotic inj. Ceftri-
axone & inj. Amikacin followed by oral cefixime for 3
days. He had gross noncompliance with injectable
antibiotics. However, he had no history of cough and
cold or history of contact with COVID-19 positive .
patient and febrile illness in other family members On
admission in our hospital baby was ill looking, irrita-
ble, afebrile, moderately pale with tachypnea (40
b/min), tachycardia (170 beat/min), normal blood
pressure (BP was 90/60 mmHg on 50th centile), SPO2
98% on room air, coated tongue, pedal oedema. He
also had neck rigidity with positive kernig sign. Skin
survey normal, no rash, no lymphadenopathy. His
lungs were clear, heart S1, S2 present with an early
diastolic murmur present in left second grade 3/6. All
jerks were intact and planter bilateral flexor.
On admission his lab investigations showed low HB
(7.3 gm/dl), TC 8.06 × 10 9/L, N-67 %, thrombocyto-
penia (platelet 110 × 10 9L/ m3) with microcytic
hypochromic anemia, high CRP(27.09mg/dl; normal
< 0.5), high D dimer (15818 µg/ L; normal : < 500), S.
Ferritin (427 ng/ml; normal :12-140), hypoalbumin-
emia (S. albumin 1.8 mg/dl), chest X ray showed opac-
ity in right sided lung. He had RT PCR for COVID- 19
negative but COVID antibody positive. His 2D and
color Doppler echocardiography revealed vegetation
(4.5mm×4.4 mm) over the pulmonary valve. Thick-
ened distorted pulmonary valve with flail leaflets with
grade II pulmonary regurgitation, no pulmonary
stenosis. Small aneurysmal dilation of left anterior
descending artery (LAD) and right coronary artery
(RCA). Dilated left main coronary artery (LMCA),
LAD 3mm (Z score +4.3; normal 0.87 to 2.2 mm),
RCA 3.4mm (Z score + 4.41; normal 1.00 to 2.48
mm), LMCA 2.8 mm (Z score + 2.2; normal 1.27 to
2.71 mm) ,mild pulmonary arterial hypertension,
Pulse Volume 13 2021
Key words: : Infective Endocarditis, Vegetation on pulmonary COVID-19,
MIS-C, Coronary Artery Aneurysm (CAA).
27
CASE SUMMARY 2
DISCUSSION
good biventricular function.Four samples of blood
culture and sensitivity (C/S) were sent on different time
according to Modified Duke Criteria 2. Blood C/S
revealed staph aureus sensitive to vancomycin. CSF
study was normal. Urine routine examination and C/S
were normal. His dengue NS1, ICT for malaria were
negative and widal test was normal. His MRI of brain
revealed normal study. We started inj meropenem,
vancomycin and methylprednisolone (1 mg/kg/dose 12
hourly). Packed RBC was given. on second day of
admission, the child developed shivering followed by
cyanosis on lips and finger, SPO2 was 96% in room air
with low blood pressure. After the patient was settled,
Intravenous Immune Globulin (IVIG) was given at a
dose of 2gm/kg. His fever subsided within 24 hours of
IVIG infusion. He was also given inj. methylpredniso-
lone for successive six days. Then oral prednisolone
started on the seventh day. Gradually the dose tapered
over 4 weeks.
Repeat echocardiography was done on 8th day of admis-
sion which revealed one vegetation on pulmonary valve
(2.4mm x2.2 mm) reduced in size, distorted thickened
pulmonary valve with flail leaflets, moderate to severe
pulmonary regurgitation, dilated left descending artery.
Follow up echocardiography confirmed reduction of
the size of vegetation within two weeks of treatment. At
5th week of treatment, we reported the disappearance of
vegetation. Notwithstanding the permanent damage to
pulmonary valve caused free pulmonary valve regurgi-
tation. The parents were counselled regarding further
follow-up.
A 3 year 6-month-old boy weighing 12 kg, height 91.5
cm, 4th issue admitted through OPD, EHD with the
complaints of high grade, irregular fever for last 4
months. Highest recorded temp was 1020 F and fever
subsided by taking paracetamol. Fever was associated
with itchy erythematous rash over both upper and
lower limbs for the last several months. He was a diag-
nosed case of congenital mild pulmonary valve steno-
sis. He had history of infective endocarditis (vegetation
on pulmonary valve) which was treated with antibiot-
ics and antifungal for four months (10.06.19 to
08.09.2019). Boy had recent history of contact with
COVID-19 positive patient in family.
On admission baby was afebrile, SPO2 98% in room
air, respiratory rate 24 breath/min, heart rate 120 b/min,
BP 100/60 mmHg, mildly pale, no lymphadenopathy,
and chest deformity present. His weight for age and
height for age was below 3rd centile. Skin survey
revealed follicular hyperkeratosis in both lower
limbs.Precordium examination revealed deformed
chest with normal findings. Abdominal examination
revealed hepatomegaly (2.5cm). On admission lab
investigation revealed microcytic hypochromic
anemia. There was also high D-dimer, high ferritin
and low vit. D level. He tested Positive for RT-PCR for
COVID.
2D and color Doppler echocardiography showed one
large (25mm x14mm) irregular, echogenic, homoge-
nous, oscillating mass (vegetation) moving along
blood flow from Right Ventricular outflow tract
(RVOT) to pulmonary artery through pulmonary valve
during systole and diastole. Stalk is attached above
pulmonary valve. Mild pulmonary valvular stenosis
(14 mmHg) and small aneurysmal dilatation of
LMCA and RCA with dilated LMCA with normal
cardiac function. Chest X ray revealed right sided
enlarged radiolucent area (? Calcified hilar lymph
node). CT pulmonary angiogram dilated main pulmo-
nary artery (MPA) measuring 2.3 cm, right pulmonary
artery (RPA) 1.5 cm and left pulmonary artery (LPA)
1.3 cm. A soft tissue structure measuring about
2.7x1.2 cm was noted at the root of the main pulmo-
nary artery, compressing semilunar valve towards left
which is the movable during systolic and diastolic
phases. Calcification (1.4 x 1.0 cm) noted in right hilar
region.
After admission he was treated with IVIG 2gm/kg
over 24 hours, inj. ceftriaxone, inj vancomycin, inj
gentamycin after sending aerobic blood culture of 5
samples from 5 different sites over 24 hours. Later on,
low dose tab aspirin was added. As second blood
culture showed Staphylococcus Saphrophyticus which
was sensitive to inj gentamycin and inj vancomycin,
we continued the same antibiotics. Subsequently,
Patient underwent surgery to remove the vegetation
and biopsy revealed Mycobacterium tuberculosis. We
started anti TB drugs along with other medications.
Infective endocarditis is the infection of endocardium
caused by different types of microbial infection1.
Although the prevalence of IE is lesser than the
congenital heart diseases, the consequences of IE are
Infective Endocarditis Associated with MIS-C Case Studies
Pulse Volume 13 2021
28
Case Study
life threatening. The population are at risk group for IE
with underlying congenital structural heart diseases
with jet flow through shunt or defective valve,
post-surgical interventions and indwelling central
venous catheter or prolonged use of venous line for
intravenous medications due to frequent hospitaliza-
tion. Damage to endocardium, vascular intima or
valve, formation of nonbacterial thrombotic endocardi-
tis (NBTE), transient bacteremia, adherence of the
bacteria or organism to the NBTE and subsequent
rapid multiplication of buried microorganism within a
vegetation is the sequence of events, which occur
because of complex interaction between microorgan-
ism and usual host immune response. Vegetation may
cause valvular damage followed by dysfunction and
shedding of vegetation itself can cause embolism as
well as ischemia, and necrosis in important tissues and
organs, resulting in high mortality rate2.
Our first child had several episodes of high spiking
temperature for last three months and was treated for
ten to twelve days each time in a hospital with intrave-
nous antibiotic as a probable case of enteric fever
nevertheless his widal test and blood culture were
negative. His compliance with antibiotics were poor.
During last episode of fever after admission in our
hospital his blood culture sensitivity test, triple antigen,
serological test for dengue and Kala-Azar were nega-
tive. Because of his high fever with irritability and
neck rigidity, he was evaluated for tubercular meningi-
tis (TB gold, CSF study, brain MRI) which were
normal.The child had spiking fever (104 ° F) for more
than one week. The child had hepatosplenomegaly with
pneumonitis in chest x-ray and neutrophilic leukocyto-
sis, high CRP, high D-dimer suggested for 2 D and
color Doppler echocardiography for exclusion of
MIS-C (Multisystem Inflammatory syndrome in Chil-
dren). However, he had small aneurysmal dilation of
LAD (Left anterior Descending artery) and RCA
(Right coronary artery) and dilated LMCA (Left main
coronary artery) as shown in Fig 1, Fig 2. In addition,
he had one non-obstructive small vegetation attached
on pulmonary valve leaflet (Fig-3). Pulmonary valve
leaflets were thickened distorted and flail which caused
severe pulmonary regurgitation (Fig 4). Pulmonary
regurgitation of the infected valve was nosis as MIS-C.
almost constant and results from a various mechanism.
Fig 1 (case1) : Left anterior descending artery (LAD)aneu-
rysm with small vegetation on pulmonary valve.
Fig 2 (case1): Aneurysmal dilation of right coronary artery
(RCA).
Such as for the destruction of pulmonary valve leaflets
and their noncoaptation due to adhesion of vegetation,
itself on pulmonary valve leaflets extending to the tip.
Although RT-PCR for COVID-19 was negative, his
positive antibody for COVID-19 emphasized the diag
Evangelista et al described in their study valvular
regurgitation because of vegetation which also
described variety of dysfunction of valve such as
noncoaptation, perforation, to complete flail leaflets.
They even described valvular perforation leading to
severe valvular insufficiency that may cause the acute
onset of heart failure3.Although our child had no signs
of heart failure because of timely diagnosis and treat-
ment.
Pulse Volume 13 2021
29
Fig3 (case 1): Small vegetation on pulmonary valve.
Fig 4 (case 1): Severe pulmonary valve regurgitation through
damaged valve.
The second child was previously diagnosed as infective
endocarditis and was treated in other hospital for intra-
venous antibiotic for four weeks. However, in our
hospital he was diagnosed clinically, by laboratory
investigations and by echocardiography as MIS-C with
infective endocarditis. He also had fever (103˚F),
neutrophilic leukocytosis, thrombocytosis, high CRP,
high D-dimer with left main coronary artery aneurysm
and large vegetation obstructing pulmonary valve (Fig
5,6).Vegetation of first child was single, small, homog-
enous, almost globular, localized on the base of the
pulmonary valve leaflets extending to tip. The shape,
consistency and lack of stalk suggested that the vegeta-
tion might be caused by staphylococcal infection. The
echogenicity of vegetation suggested that the lesion
was caused by the microbial infection not more than
two weeks1. The vegetation of the second child was
large, diamond shaped, homogenous more echogenic
which suggested formation of vegetation for prolonged
time (Fig 5).
Fig 5 (case 2 ): Large vegetation on pulmonary valve leaflet.
Fig 6 (case 2): Coronary artery aneurysm of left main
coronary artery (LMCA) with vegetation on pulmonary
valve.
In addition, the child had congenital deformed pulmo-
nary valve with stenosis over which the vegetation
developed. The site of adherence of vegetation indicat-
ed that the traumatized valvular endothelium acted as
nidus of microbial infection due to high velocity jet
flow of blood through stenosed valve. Chest x-ray and
slice CT suggested calcification of hilar lymph nodes.
Blood culture reports revealed the growth of staphylo-
coccus aureus in first case and staphylococcus sapro-
phyticus in second case. The sequence of formation of
vegetation leads to adhesion and entrapment of bacte-
ria inside of NBTE and multiplication of microorgan-
ism increases the size. For the S. aureus these adhe-
sions have been termed MSCRAMMs (microbial
surface components recognizing adhesive matrix
molecules1.
Echocardiography is the confirmatory investigation to
determine number, size, shape, location, echogenicity
and mobility of vegetation. It is also useful for predic-
tion of embolic risk. Both of the cases met Modified
Infective Endocarditis Associated with MIS-C Case Studies
Pulse Volume 13 2021
30
Case Study
Duke Criteria to be diagnosed as definitive case of
infective endocarditis1. But we did cardiac multi slice
CT (MSCT) in second case to determine accurate
analysis of size, anatomy, calcif ication, abscess, infarc-
tion, any concomitant pulmonary vascular disease or
embolism, even in distal pulmonary vasculature4.
Sensitivity, specificity, diagnostic accuracy, and prog-
nostic implications of the M-mode echocardiographic
pattern of vegetation were examined prospectively in
consecutive patients referred with potential active
infective endocarditis (IE). It is useful to do 3D echo-
cardiography for diagnosis of exact anatomy and
location of vegetation which was done in first case. We
did not need to do TEE (Trans esophageal echocardiog-
raphy). It is reported that TEE is mandatory for evalua-
tion of pacing or ICD leads vegetation5.
In addition to infective endocarditis, both of the child
developed MIS-C due to COVID-19, which was
confirmed clinically, COVID antibody positive for the
first case and by RT-PCR positive test for 2ndcase. RT-
PCR positive indicated infection with COVID-19
within last two weeks whereas COVID antibody
positive meant the patient had corona virus infection
within last two to three months. Both of the lab results
revealed recent contact or infection with COVID-19.
However, for the first case, contact or infection by
COVID-19 virus within few months could be the cause
of inflammation of pulmonary valve, which acted as
the nidus of vegetation. Repeated hospital admission
and taking intravenous antibiotics by prolonged use of
same intravenous line at hospital and even at home
without proper hygiene maintenance could be the
reason of bacterial infection results in infective endo-
carditis. We suspected the deformed valve is due to
vegetation of infective endocarditis, as he had no
murmur during his previous follow up with Pediatri-
cian since birth. Nor withstand, he did not have any
previous echocardiography report, which revealed his
normal pulmonary valve.
Kumanayaka et al described a case study of infective
endocarditis induced by COVID-19 infection. They
described that COVID-19 was the cause of hyperactive
inflammatory response along with hypercoagulable
state leading to various complications6. Both of our
children were admitted with recent history of fever.
They were diagnosed clinically, by serological reports
and echocardiography documents as MIS-C.
They had small aneurysmal dilation of all coronary
arteries. The coronary architecture were almost
smooth which revealed the inflammation were within
two weeks7.Coronary artery internal diameter were
taken and plotted in z-score (Boston criteria) and
classified as AHA guideline of Kawasaki disease8.
Different blood samples sent on different time from
different sites showed staphylococcus aureus and
staphylococcus saprophyticus in blood culture. For the
first patient according to culture sensitivity test we
could complete intravenous ceftriaxone and vancomy-
cin for 6 weeks. Meanwhile, we saw the clinical
improvement of the child. Echo revealed the gradual
reduction and disappearance of vegetation. However,
the damage of the pulmonary valve was permanent
which caused free pulmonary regurgitation.
Nevertheless, for the second patient there was surgical
indication for removal of vegetation because of the big
size (>10mm) (Fig 5), pulmonary valvular obstruction
and also nonresponsive to medical therapy even after 4
weeks. As the child was diagnosed clinically as MIS-C
with fever more than 3 days, neck rigidity and respira-
tory distress coronary aneurysm with evidence of
coagulopathy and elevated markers of inflammation
(raised CRP) the child was treated with IVIG, intrave-
nous methylprednisolone. But tab aspirin was not
given. Because anticoagulation (aspirin) is controver-
sial during treatment of native valve infective endocar-
ditis due to increased risk of cerebral hemorrhage
because of association with cerebral septic embolism9.
Their fever subsided within 24 hours of IVIG infusion.
Coronary artery aneurysms were normal in caliber
within seven days. Both of these children were on
follow up according to CDC and WHO protocol10,11.
The second patient needed surgical removal of vegeta-
tion after completion of intravenous antibiotic for six
weeks. As there was no change of shape, homogeneity
or reduction of size of vegetation. Perioperative biopsy
of vegetation revealed mycobacteria tuberculosis.
The first child with flail pulmonary valve with severe
pulmonary regurgitation is on follow up with medical
management. He has no clinical or echocardiographic
evidence of right heart impairment. The second patient
is fully cured after surgery and completion of anti TB
medicine and intravenous antibiotics for six weeks.
Pulse Volume 13 2021
Pulse Volume 13 2021 31
CONCLUSION
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Infective Endocarditis Associated with MIS-C Case Studies
