Dengue Infection and Cardiac Manifestations How Important? Certainly greatly affect the clinical course of dengue patients with viremia phase - critical phase and recovery phase. Cardiac Manifestations, as an important organ that determines stable hemodynamics. What if our heart is disturbed? of course there is influence in management and prognosis. Please refer to this power point.

1. RESOURCE PERSON : DR. dr. Soroy Lardo, SpPD. FINASIM
Division of Tropical Medicine and Infectious Diseases
Indonesia Army Central Hospital Gatot Soebroto
 Resource person : d. soroy lardo finasim
JOURNAL READING
Nuriza Karuniawan
PPDS Kardiologi FKUI

2. OUTLINE
 INTRODUCTION
 CARDIAC INVOLVEMENT
 VASCULAR INVOLVEMENT
 CARDIOVASCULAR THERAPEUTIC TARGET
 CONCLUSION

3. Introduction
 Dengue is currently one of the most important emerging infectious
diseases in the world
 Dengue virus (DENV 1-4), genus Flavivirus, family Flaviviridae
 Dengue is transmitted by mosquitoes of the genus Aedes, reported in
>100 countries,
 High disease burden across South and Southeast Asia
 Shock more frequent in children, bleeding and organ impairment more
common in adults

4. Introduction
 Mild disease  severe(1–5%) organ impairment, bleeding, and plasma
leakage (DSS)
 The increase in capillary permeability is the best known cardiovascular
complication associated with dengue
 Other cardiac manifestations : rare fulminant myocarditis to more-
common associations with functional myocardial impairment and
arrhythmias

5. Classification System

6. Clinical Course of Dengue

7. Cardiac Involvement
 Cardiac manifestation of Dengue : impairment myocardial function,
arrhythmia, myocarditis
 Myocarditis
 Dengue Myocarditis
 Dengue in elderly
 Evidence of cardiac manifestations of Dengue in three perspective
 Functional
 ECG
 Pathology

8. Functional Studies
 Dengue infection is associated with transient, self-limiting myocardial
dysfunction

9. Pathogenic Mechanism Cardiac
Dysfunction in Dengue
 In majority, direct viral invasion of cardiomyocytes is unlikely

10. Functional Studies
 Fulminant dengue myocarditis might represent a separate phenomenon
in which host genetics or increased cardiotropism of the virus allow
widespread myocyte infection and damage
 Reports of dengue epidemics
 DENV 1-3
 Primary or secondary DENV infection
 Pericardium : dengue pericarditis, pericardial effusion
 Increased plasma leakage
 Less frequent

11. ECG Studies in Dengue Infection
 ECG changes are often transient and non specific
 Bradyarrhythmia : sinus bradycardia, first- and second degree AV Block, VES
 Tachyarrhythmia : AF
 Non specific ST-T changes
 Occur during any phase of the disease and fairly common (30-44%)
 Mechanism
 Altered autonomic tone
 Electrolyte and calcium derangements
 Subclinical myocarditis
 Clinical relevance remains speculative

12. Clinical Course of Dengue

14. VES and Altered Calcium Homeostasis
in Dengue
 Increased Calcium concentration during
diastolic phase in Dengue infection

15. Functional Studies

16. Pathological Studies
 Histopathological studies limited only in autopsy
studies
 Results : interstitial oedema, inflammation, and
myocardial necrosis fulminant myocarditis
 Dengue capsid protein was demonstrated to be
present in cardiomyocytes, interstitial cell,
myoblast
 another finding : clusters of viral particles were
identified inside cardiomyocytes widespread
necrosis and interstitial oedema

17. Vascular Involvement
 Increased systemic vascular permeability and plasma leakage  critical
determinant disease severity
 Coagulopathy
 Endothelial activation
 soluble thrombomodulin,
 intercellular adhesion molecule 1
 vascular cell adhesion protein 1
 E-selectin

18. Clinical Features of Vasculopathy
Increased permeability
Splanchnic Circulatory Changes
Bleeding

19. Increased Permeability
 Profound in children and young adult; lesser degree is difficult to identified
 strain gauge plethysmographyassess filtration capacity (Kf)an overall
measure of microvascular permeability
 A study in Vietnamese children with DSS or DHF without shock
 increased Kf in both groups
 individual’s compensatory reserve ability to upregulate homeostatic
mechanisms to balance the intravascular volume loss
 healthy children have higher Kf than healthy adults
 higher number of developing capillaries  more vulnerable to leakage than
mature capillaries

20. Increased Permeability
 evidence ultrasound study
 transient increase in capillary permeability (febrile phase,day 2–3)
 more common in secondary infections
 Another study, similar proportion of patients with primary infections and
those with secondary infections (32% and 40%, P = 0.69)
 pleural effusions, ascites, and gallbladder wall oedema are commonly
present during the critical phase of dengue and correlate with disease
severity
 plasma leakage seems to be broad (mildsevere) and in primary, or
secondary infections, and start earlier than previously understood

21. Increased Permeability
 Capillary leak in DENV infection is slow and persistent  narrow pulse
pressure
 Pulse pressure < 20 mmHg + impaired perfusion  DSS
 Close observation for signs of plasma leakage is critical from the end of
the febrile phase
 haemoconcentration, determined by tracking changes in serial
haematocrit measurements (insensitive)

22. Splanchnic Circulatory Dysfunction
 An ultrasound study of 45 patients with dengue
 a dilated portal vein with lower flow velocity
 a higher congestion index
 a smaller inferior vena cava in patients with DSS than in those with DF or DHF
without shock
(hepatosplanchnic circulatory dysfunction)

23. Bleeding
 Mucosal bleeding, skin pethecie, and bruishing
 coagulation abnormalities evolve during the various phases of the
infection and correlate with vascular leakage severity rather than bleeding
 Mechanism
 loss of anticoagulant proteins through capillaries leak
 endothelial activation  increased thrombomodulin and other procoagulant
factors
 viral induction of plasminogen
 release of a heparin-like circulating anticoagulant from the microvascular
surface

24. Pathogenesis of Vasculopathy
 viral and NS1 interactions with the surface glycocalyx layer
 endothelial glycocalyx layer
 negatively charged mesh of glycoproteins
 Proteoglycans
 glycosaminoglycans
 glycocalyx layer : primary barrier to the movement of water and other
molecules out of the microcirculation
 NS1 + heparan sulfate (major glycosaminoglycan)disruption 
increased vascular permeability.

25. Cardiovascular therapeutic targets
 No antiviral agents
 Supportive,cautious fluid resuscitationadequate tissue perfusion during
the critical period of capillary leakage
 Rarely, inotropic support is required
 No cardiac-specific treatments for dengue myocarditis
 standard treatment for cardiac failure (β-blockers, angiotensin-converting-
enzyme inhibitors, and diuretics
 Antiviral and immunomodulatory treatments, interferon beta, corticosteroids,
and intravenous immunoglobulins(?)

26. Cardiovascular therapeutic targets
 No benefit with corticosteroids in order to modulate plasma leakage
 A study of lovastatin in early dengue is ongoing in Vietnam
 antiviral properties
 stabilizing and anti-inflammatory effects on the endothelium
 upregulation of endothelial nitric oxide synthase  might help to restore
endothelial function and microvascular tone and integrity

27. Conclusion
 Dengue is broad, ranging from myocardial impairment and arrhythmias to
vascular barrier dysfunction causing plasma leakage and haemodynamic
compromise.
 Myocardial impairment can contribute to haemodynamic instability during
the critical phase of capillary leakage.
 Pathogenesis studies are needed to address the underlying mechanisms of
capillary leak and endothelial dysfunction so that effective therapeutic
targets can be identified
 echocardiography should be performed in patients with dengue,
particularly in those with severe disease and refractory shock