INFLUENZA IN HEART FAILURE :

BAD COMBINATION

Galih Rakasiwi S
Meity Ardiana

Dep/SMF Kardiologi dan Kedokteran Vaskuler

FK Unair/RSU dr. Soetomo
Surabaya
2016 1
 CONGESTIVE HEART FAILURE

Heart (or cardiac) failure is the state in which the

heart is unable to pump blood at a rate
commensurate with the requirements of the tissues
or can do so only from high pressures

Braunwald 10th Edition,

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SIGN & SYMPTOMS

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 INFLUENZA
Influenza (the flu): contagious respiratory illness the caused by
influenza viruses
In virus classification influenza viruses are RNA viruses that make up
three of the five generation of the family Orthomyxoviridae.

Influenza Virus A
Influenza Virus B
Influenza Virus C

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 INFLUENZA STRAINS

Type Natural Reservoir Animals affected Disease Epidemic in Humans

A waterfowl humans, pigs, chickens flu and flu complications yes
B unknown mostly humans only flu and flu complications yes
C unknown humans mild respiratory illness no
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INFLUENZA A VIRUSES

are classified into subtypes based on antibody

responses to HA and NA. These different types of
HA and NA form the basis of the H and N
distinctions in, for example, H5N1. There are 16 H
and 9 N subtypes known, but only H 1, 2 and 3, and
N 1 and 2 are commonly found in humans.
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TRIGGER OF ACUTE HEART FAILURE IN CHRONIC
HEART FAILURE
The main factors that precipitate decompensation and
hospitalization include failure to follow the treatment, acute
myocardial ischemia, high blood pressure and respiratory
infections such as pneumonia and viral diseases
Pulmonary congestion is present in most patients with HF and
predisposes them to respiratory infections.
The causal relationship between respiratory infection and
clinical decompensation has been confirmed in several
epidemiological studies.
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BMC Public Health 2008, 8:59

 Respiratory tract infections were associated with acute
exacerbations of heart failure, however, the role of the
influenza virus, a major agent of such infections.
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 TRANSMISSION

Droplet Spread
from a persons cough or sneeze
person touches respiratory droplets on another
person or object and then touches their own mouth
or nose
Aerosol 100,000 TO 1,000,000 virions per
droplets
Incubation period = 1-4 days (avg. = 2 days)
Adults infectious from day before symptoms begin to 5
days after illness onset
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CDC 14
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 COMPLICATIONS
Deaths Result from pneumonia and/or worsening of cardiopulmonary conditions
and other chronic diseases
Influenza can exacerbate underlying medical conditions, including CVD and
diabetes, and can also lead to viral pneumonia, secondary bacterial pneumonia, or
a coinfection with other viruses or bacteria.
Epidemiological data indicate that risks for complications, hospitalizations, and
death from influenza are higher for individuals at the extremes of age (<5 years
old, >65 years old) and for persons with chronic medical conditions than for
healthy older children and younger adults
 INFLUENZA IN HEART FAILURE
Influenza can produce a potent inflammatory and thrombotic stimulus,
with either direct myocardial injury or indirect influence by activation of
circulating procoagulants, elevation in cytokine levels, endothelial
dysfunction, fluid shifts and sympathetic stimulation as observed in
patients with coronary artery disease, stroke and heart failure.
The immune system protects the host from infection with influenza
virus.
Therefore, the pathogenesis of influenza virus depends on the function of
the immune system. 17
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 VACCINE

inactivated (administered intramuscularly) only subvirion

and purified surface antigens are used
a live, attenuated form (administered intranasally) it has
not been approved for use in persons with CVD or other
conditions that increase the risk of influenza-related
complications.

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 ADVERSE EVENTS

Intramuscular Injection (TIV) Nasal Spray (LAIV)

Local Reactions: Local Reactions:
cough 14%
pain 20-50% runny nose 45%
sore throat 28%
redness 10-13% chills 9%
swelling 6-8%
Muscle aches: 18-30%
Headache: 14-30%
Malaise: 14-22%
Fever: 2-3%
Allergic reactions:
Guillain Barre Syndrome:
1 in 1 million
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 IN SUMMARY.

Influenza is one of triggering factor of acute heart failure

Influenza vaccine in high-risk patients is of paramount importance
and could prevent influenza-related hospitalizations, reduce MACE
and acute heart failure and decrease mortality

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THANK YOU

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 ECONOMICS

Annual direct medical cost = $4.6 billion

Total direct and indirect costs = $12 billion (indirect includes work days lost, school
days lost, etc.)
Vaccination can reduce these costs from hospitalizations, lost work days and
antibiotic use.
 ANTIVIRAL MEDICATIONS

4 medications:
Amantadine: orally administered, treats type A
Rimantadine: orally administered, treats type A only for adults
Oseltamivir-capsule, treats type A & type B
Zanamiv-inhaled powered drug, treats type A& type B

Last for 5 days and must be started w/in the 1st 2 days of
illness
Used to control outbreaks in institutions
 ANTIGENIC DRIFT

HA and NA accumulate mutations

RNA virus

immune response no longer protects fully

sporadic outbreaks, limited epidemics

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 HOW FLU VACCINES ARE MADE

Egg based Flu vaccines- over 70 years most common way. CDC grows the viruses or in
eggs, then provides them to manufacturers that inject them into fertilized hens eggs-
incubated then harvested either inactivated (killed) for flu shots, Or attenuated live
viruses used in nasal spray
Cell based Flu vaccines- since 2012. CDC egg grown viruses are grown next in cultured
mammalian cells and the fluid is removed and viral antigens purified. Less eggs required,
quicker manufacturing period
Recombinant Flu vaccines- since 2013. Does not require chicken eggs, antibiotics, etc at
all. Influenza HA protein - which induces immune response in people, is combined with
another partial virus and grown in the lab. Only 100% egg free vaccine
 ANTIGENIC SHIFT

new HA or NA proteins

pre-existing antibodies do not protect

may get pandemics

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 WHO SHOULD NOT GET
THE FLU SHOT
Anyone who has previously experienced severe lower respiratory symptoms within 24 hours of
vaccination
Anyone allergic to any component of the vaccine
Anyone who had a serious reaction to a previous flu shot
Anyone who developed Oculo-respiratory syndrome (ORS) with lower respiratory tract symptoms*
Anyone who developed Guillain-Barre syndrome (GBS) within 6 weeks of previous influenza
vaccination*
Anyone with serious acute illness
Egg allergic individuals may be vaccinated against influenza using TIV or QIV however, as with all
vaccine administration, immunizers should have necessary equipment to be prepared to respond
to a vaccine emergency

*Seek medical advice prior to vaccination

 DURATION OF SERUM ANTIBODY RESPONSE
TO SEASONAL INFLUENZA VACCINES:
SUMMARY
The level of antibody response made to seasonal influenza vaccines depends on the
vaccine preparation, dose, prior antigenic experience, and age or underlying
disease conditions of an individual

Antibody responses are typically greatest among primed healthy older children,
adolescents and young adults and are lower among the elderly and young children

Following vaccination, anti-HA antibody titers (measured by the hemagglutination-

inhibition assay) peak 2- 4 weeks post-vaccination in primed individuals but may
peak 4 weeks or later in unprimed individuals or older adults

Serum antibody titers may fall by 50% or more by 6 months after vaccination, with
the degree of reduction being proportional to the peak titers achieved

Vaccine-induced serum antibody titers then remain stable for two to three years
 BEWARE OF TYPE A

15 known HA subtypes: H1-H15

9 known NA subtypes: N1-N9
While all subtypes can be found in birds, only H1-H3 and N1-
N2 are known to circulate widely in humans.
H1-H3 are the only types known to have caused pandemics
in humans
Pandemics arise from flu strains that have novel HA and NA proteins
that people have no immunity to
 TYPES OF FLU VACCINES
Fluzone Trivalent Vaccine (IM) egg based, contain two A viruses and one B virus (>6 months)
Fluzone Quadrivalent- (IM) egg based, contain two A viruses and two B viruses (>6 months)
Fluzone High-Dose Vaccine- (IM Trivalent) - has more 4x more antigen to stimulate immune response,
indicated for >64 years. The trade off is this year it is only a trivalent vaccine, next year will be
quadrivalent. 2014 NEJM study showed 25 % reduction in illness in seniors compared to standard trivalent
vaccine
Fluzone Intradermal Quadrivalent- very tiny needle !!!(age 18 to 64 years). Available at Target
pharmacies
FluMist Quadrivalent (intra-nasal spray) egg based, attenuated live virus for healthy, non-pregnant
people age 2-49.
Flublok -Trivalent Recombinant Infl. Vaccine (RIV3) for egg allergic > 18 years. Available at Target
Pharmacies .covered by insurance
When compounded by hypoxemia, influenza may exacerbate underlying
cardiovascular disease, resulting in volume overload HF, plaque rupture,
arrhythmia, with potentially lethal cardiovascular consequences.

Influenza infection has also been associated within direct myocardial

depression, which has been ascribed to an increase in pro- inflammatory
cytokines; with histologic evidence of myocardial injury, myocarditis and
myocyte necrosis after influenza- related deaths

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influenza immunization in high-risk patients with cardiovascular disease is of
paramount importance and could prevent influenza-related hospitalizations,
reduce MACE and acute HF and decrease mortality.

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 TYPE A TYPE B TYPE C

severity of illness ++++ ++ +

animal reservoir yes no no
human pandemics yes no no
human epidemics yes yes no (sporadic)
antigenic changes shift, drift drift drift
segmented genome yes yes yes
amantadine, rimantidine sensitive no effect no effect
zanamivir sensitive sensitive
surface glycoproteins 2 2 (1)

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Re-assortment occurs when humans or pigs are co-infected with both avian and
human influenza subtypes, giving rise to a novel virus with efficient human-to-
human transmission while having avian surface proteins.
Studies have implicated re-assortment as the cause of the 1957 and 1968
pandemics(11,12), while the 1918 Spanish flu strain is postulated to be a direct
adaptation of an avian subtype(13

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 Hemagglutinin & Neuraminidase

Hemagglutinin (HA) and neuraminidase (NA) are the two

large glycoproteins on the outside of the viral particles. HA is
a lectin that mediates binding of the virus to target cells and
entry of the viral genome into the target cell, while NA is
involved in the release of progeny virus from infected cells, by
cleaving sugars that bind the mature viral particles.

Thus, these proteins are targets for antiviral drugs.

Furthermore, they are antigens to which antibodies can be
raised.

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 MECHANISM OF INFECTION
The mechanism through which influenza may cause cardiovascular events
is not well understood.
One current hypothesis is that the inflammatory response of the body to
viral infection leads to production of autoantibodies to modified low-
density lipoprotein, which causes the development and progression of
atherosclerotic vascular injury.
Another current hypothesis is that direct colonization of the vessel wall
initiates local cell autoimmune reactions by activation of antigen-
presenting cells

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ANTIGENIC DRIFT ANTIGENIC SHIFT
HA and NA accumulate mutations new HA or NA proteins
RNA virus pre-existing antibodies do not
immune response no longer protects protect
fully may get pandemics
sporadic outbreaks, limited epidemics

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 VACCINE INFORMATION
Intramuscular Injection (TIV): Effectiveness in adults < 65 years
80% (95% CI 56% to 91%) when vaccine matched circulating strain.
50% (95% CI 27% to 65%) when not well matched.
Jefferson, et al. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD001269.

Intradermal Injection (ID): Effectiveness in adults 18 64 years

Similar efficacy to TIV against influenza A (H1N1), A (H2N3) and B strains.
Sanofi Pasteur, Inc. Fluzone [package insert]. 2011

Nasal Spray (LAIV): Effectiveness in healthy adults

85% overall efficacy in preventing laboratory-documented influenza.
Treanor et al., Vaccine 1999;18:899906.

Nichol et al., JAMA 1999;282:13744. 47

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 SIDE EFFECTS TO INACTIVATED
VACCINE
Soreness at vaccination site
Fever, malaise, myalgia
Guillain Barre Syndrome: 1 additional case per 1 million
people
Body's immune system attacks part of the nervous system and
results in weakness or tingling sensations in the legs that can
spread to the arms and upper body.
Can result in paralysis
 MECHANISM OF INFECTION

Mechanism through which influenza may cause cardiovascular events is

not well understood.
Inflammatory response of the body to viral infection leads to production
of autoantibodies to modified low-density lipoprotein, which causes the
development and progression of atherosclerotic vascular injury.
Direct colonization of the vessel wall initiates local cell autoimmune
reactions by activation of antigen-presenting cells

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