Johnson Francis, MD, DM
Baby Memorial Hospital, Kozhikode, Kerala, India. PIN:
673004
Address for Correspondence: Prof. Dr. Johnson Francis,
MBBS, MD, DM, FCSI, FACC, FRCP Edin, FRCP London, Senior
Consultant Interventional Cardiologist, Baby Memorial
Hospital, Kozhikode, Kerala, India. PIN: 673004. E-mail:
pulikkottil2002@hotmail.com
Abstract
There is a wide variation in the reported incidence of
cardiac involvement in dengue due to the difference in the
criteria used to identify cardiac involvement. Most common
cardiac rhythm abnormality noted was sinus bradycardia, which
was often self limited. Fulminant and fatal myocarditis have
been documented in a few cases; though in general, most cases
with cardiac manifestations improve with supportive care. Only
about one tenth of patients with biomarker elevation had
evidence of depressed left ventricular systolic function on
echocardiography. Higher incidence of depressed left
ventricular ejection fraction was noted in dengue shock
syndrome.
Keywords: dengue fever, dengue hemorrhagic fever,
dengue shock syndrome, expanded dengue syndrome, myocarditis
Dengue fever is a viral infection transmitted by mosquito
vector
Aedes aegypti. It has a wide spectrum of
manifestation ranging from very mild disease to life
threatening dengue shock syndrome (DSS) [1]. Dengue fever
patients having cardiac manifestations come under the category
of expanded dengue syndrome (EDS), which may have involvement
of other systems like nervous system or gastrointestinal
system as well.
In a recent single centre report from North India, only 1 out
of 115 cases had evidence of myocarditis [1]. This patient had
an initial ejection fraction of 40% which rose to 56% at
hospital discharge. Clinical presentation was with fever and
breathlessness. Features of congestive heart failure were
noted on physical examination. There was sinus tachycardia on
ECG; X-ray showed bilateral pleural effusion, echocardiography
revealed mild pericardial effusion and global left ventricular
hypokinesia. Decongestive therapy, inotropic support and
platet transfusions were given and there were no long term
sequelae on follow up.
Dengue myocarditis may not respond well to management in all
cases. Fatal dengue myocarditis despite support with
extracorporeal membrane oxygenator (ECMO) has been documented
by Yee-Huang Ku et al [2]. This patient was hemodynamically
unstable, had ST-T changes on ECG and rising Troponin I
levels. Echocardiography had shown hypokinesia of anteroseptal
region of the left ventricle with ejection fraction of 34%.
Coronary angiography showed patent coronary arteries. Arterial
blood gas analysis showed severe metabolic acidosis and high
lactate levels. Intra aortic balloon pump (IABP) and ECMO were
used as there was poor response to three vasopressors.
Ejection fraction deteriorated to 10% and severe pulmonary
edema occurred. Patient died on 6th day in spite of all
supportive measures. Another case of fulminant dengue
myocarditis with shock and fatal outcome despite IABP support
was reported by Lin TC et al [3].
A study of 100 cases of dengue from South India specifically
looking at cardiac manifestations could not document any case
with echocardiographic evidence of myocarditis [4]. At the
same time 32 of them had sinus bradycardia, which was noted to
be the commonest rhythm abnormality in their series. This is
also the observation at author's institution during a recent
epidemic of dengue (unpublished observation). Ventricular
bigeminy, ventricular trigeminy and ventricular tachycardia
were noted in one patient each. AV dissociation with sinus
node dysfunction was noted in another. All these changes
reverted within 24 hours. Abnormalities of ST segment and T
waves were noted in 11 patients.
In another study from South India involving 120 patients,
cardiac manifestations were noted in 44 [5]. But this study
had a broad definition of cardiac manifestations, including
rhythm disturbances, changes in heart rate, raised cardiac
enzymes, abnormal ECG and echocardiogram. In sharp contrast
with the previous study, sinus bradycardia was noted only in
10 (8.77%). ST-T changes were noted in 4, first degree AV
block in 4 and right bundle branch block in 2. All these
abnormalities were transient. 28 patients had both CK-MB and
troponin I elevation; 12 had isolated CK-MB elevation and 4
had isolated troponin I elevation. But the cut off value for
CK-MB was taken as 25 and that for troponin I as 0.04, both
being just the upper limit of normal. None of the patients in
this study had significant echocardiographic abnormalities.
Twenty percent incidence of myocarditis among 300 cases of
dengue was reported from Eastern India [6]. Other studies from
different parts of India have also reported myocarditis as
part of EDS [7, 8]. A report from Sri Lanka stated that there
were 35000 cases of dengue during an out break in the country,
of which 340 died. This study focussed on the 15 cases of
dengue which occurred during pregnancy, of which one had
myocarditis, but recovered with supportive measures [9]. Only
one case of myocarditis was noted among 560 dengue patients at
Martinique (Caribbean Island) [10]. In another report, 10.7%
of 102 pediatric patients from Colombia with dengue
hemorrhagic fever had myocarditis [11]. So it can be seen that
the reported incidence of myocarditis varies widely between
geographic regions and different studies.
Troponin I and N terminal fragment of B-type natriuretic
peptide (NT-proBNP) were checked in 81 dengue patients by
Miranda CH et al from Brazil [12]. 12 were found to have
elevated cardiac biomarker levels. Ten of them underwent
echocardiography and left ventricular dysfunction was noted in
one, while 2 had regional wall motion abnormalities of the
left ventricle and another had pericardial effusion with
tamponade. Tamponade resolved after pericardiocentesis.
Evidence for cardiac involvement was further confirmed by
cardiac magnetic resonance imaging in these 4 patients. Two
patients died before imaging could be obtained, but had
necropsy findings were compatible with myocarditis. Dense
staining of mononuclear cells were noted on immunochemistry
for dengue virus in the myocardial specimens. Eight of the 12
patients had presented with clinical manifestations suggestive
of cardiac involvement: 4 with heart failure, 3 with chest
pain and 3 with hypotension and shock.
Radionuclide ventriculography in addition to ECG and
echocardiography has been used to evaluate cardiac function in
dengue [13]. Eight of the 17 patients studied had DSS while
the rest had dengue hemorrhagic fever. Seven patients had left
ventricular ejection fraction below 40% and 12 had global left
ventricular hypokinesia. 99m Tc-pyrophosphate imaging was done
in 4 patients initially, but no myocardial necrosis was
demonstrated and further such imaging was discontinued. Five
of the 8 patients with DSS had ejection fraction below 40%.
ECG changes and left ventricular function reverted to normal
within 3 weeks in this study.
One of the largest published studies on dengue myocarditis was
from the outbreak which occurred in China in 2014 [14]. Of the
total 1782 cases admitted at a single centre, 201 were
diagnosed with myocarditis (11.28%). Diagnosis of myocarditis
was made according to 2013 European Society of Cardiology
position statement for myocarditis [14]. It is heartening to
note that there were only 2 deaths in this large study. One of
them was a sudden death while another died of severe heart
failure.
In conclusion, cardiac involvement in dengue can vary from
just biomarker elevation to severe fulminant fatal
myocarditis. Whether sinus bradycardia which is the most
common cardiac manifestation in dengue, can be taken as a
feature of myocarditis is debatable. Most cases of dengue
myocarditis make a good recovery with supportive intensive
care, while an occasional patient can succumb to the illness.
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