Transcript Out-patient Management of Pulmonary Hypertension

Out-patient Management of
Pulmonary Hypertension
Jameel A. Al-Ata, MD
KAAUH & KFSH&RC-JED.
Taif 14th annual cardiovascular conference , march 2006.
Content

Definition & Types

Epidemiology

Pathophysiology

PHTN & CHD
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Concepts & Goals of
management

Workup

Management Strategies

Conclusion.
Definition & Types

Pulmonary hypertension is defined as
a mean pulmonary artery pressure
greater than 25 mm Hg at rest , or
greater than 30 mm Hg during
exercise.
WHO classification 1998
Pulmonary arterial
hypertension;

1.1 Idiopathic pulmonary hypertension

1.2 Familial
Cont”

1.3 Associated with:
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Collagen vascular disease
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Congenital systemic to pulmonary shunts
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Portal hypertension
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HIV infection

Drugs (anorexigens)/toxins
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Other thyroid disorders: Gaucher disease,
hereditary haemorrhagic telangiectasia,
haemoglobinopathies
Cont”
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1.4 Persistent pulmonary hypertension
of the newborn
1.5 Pulmonary veno-occlusive disease
Pulmonary hypertension with
left heart disease;

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2.1 Left sided atrial or ventricular
heart disease
2.2 Left sided valvular disease
Pulmonary hypertension associated with
disorders of the respiratory system
and/or hypoxaemia;

3.1 Chronic obstructive pulmonary
disease

3.2 Interstitial lung disease
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3.3 Sleep disordered breathing
Cont”
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3.4 Alveolar hypoventilation disorders
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3.5 Chronic exposure to high altitude
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3.6 Neonatal lung disease
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3.7 Alveolar-capillary dysplasia
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3.8 Other
Pulmonary hypertension due to
chronic thrombotic and/or embolic
disease;

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4.1 Thromboembolic obstruction of proximal
pulmonary arteries.
4.2 Obstruction of distal pulmonary arteries
– – Pulmonary embolism (thrombus, tumour,
and/or parasites).
– – In situ thrombosis.
Miscellaneous,
e.g. Sarcoidosis
Genetics & Epidemiology;

6% of primary pulmonary hypertension cases are
familial.

The disease is inherited as an autosomal dominant
with incomplete penetrance.

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The gene has been mapped to chromosome 2q 33
and recently identified as a mutation of the BMPR2
gene (bone morphogenetic protein receptor)
Mutations of the gene encoding BMPR-II are also
seen in at least 26% of sporadic cases of PPH.
CONT”
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Primary pulmonary hypertension (PPH)
has an incidence of 1-2 per million per
annum.
Other causes of pulmonary arterial
hypertension may account for a
further 1-2 cases per million per
annum.
Cont”
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In a 1965 series of 35 patients with primary
pulmonary hypertension 22 (63%) patients died in
the first year after the onset of symptoms.
In 1995, the median survival in a series of 18
children with primary pulmonary hypertension was
4.12 years.
With new diverse medications 90% survival at 4
years in children with severe idiopathic pulmonary
hypertension was reported with prostacyclin.
Cont”

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Without appropriate treatment, the natural
history of IPAH is progressive and fatal.
In contrast, the natural history of pulmonary
hypertension from congenital heart disease
has a broad range of survival, ranging from
months to decades.
Pathophysiology;


The constituent cells of the vessel walls
appear to undergo changes in phenotype
which in turn alter their structure and
function. ( proliferation ).
Pulmonary hypertension is associated with
pulmonary arterial thrombosis and a
hypercoaguable state associated with a
fibrinolytic defect and haemostatic
disturbance. ( thrombosis ).
Cont”

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Vasoconstriction plays an important role in
the pathogenesis of pulmonary hypertension
specially in hypoxemic patients.
In young children, pulmonary vascular
disease can progress so rapidly due to
severe obstructive intimal proliferation,
Cont”
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Lung hypoplasia.

Lung fibrosis.
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Chronic thromboembolism.
PHTN & CHD
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The age at which these lesions cause irreversible
pulmonary vascular disease varies from months to
decades.
Patients with ventricular septal defect or patent
ductus arteriosus do not develop irreversible
pulmonary vascular changes before 1 year of age.
Children with Down’s syndrome may have an
increased risk of pulmonary hypertension.
Cont”
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Infants with an atrial septal defect or
ventricular septal defect with chronic lung
disease have an increased risk for the early
development of severe pulmonary vascular
disease.
Patients with atrioventricular septal defect
may develop irreversible pulmonary vascular
disease earlier than patients with other leftto-right shunt lesions.
Cont”

Hypoxaemia with increased shunting in patients
with cyanotic congenital cardiac lesions are potent
stimuli for the rapid development of pulmonary
vascular disease.
Examples include;
1) Transposition of the great arteries, 2) Truncus
arteriosus, and 3) Univentricular heart with high
flow.
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Palliative shunting operations ( e.g. central aortopulmpnary shunts ) may lead to the development of
pulmonary hypertension.
Eisenmenger syndrome;

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Increased pulmonary vascular resistance.
Bidirectional or right-to-left shunting
through a systemic-to-pulmonary
connection, such as a ventricular septal
defect, patent ductus arteriosus,
univentricular heart, or aortopulmonary
window characterises this syndrome.
Cont”
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Prognosis of Eisenmenger patients
with syndrome is much better than for
patients with idiopathic pulmonary
arterial hypertension.
Syncope, right heart failure, and
severe hypoxemia have been
associated with a poor prognosis.
Concepts & Goals of
management;
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Confirm the diagnosis of pulmonary
hypertension.
Treat the underlying cause.
Determine the type of disease according to
the new classification, assess the suitability
of possible treatments.( must include
assessment of acute vasodilation response).
Cont”
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Monitor response to therapy.
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Reverse back to an operable state.
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Reduce the post operative risk of PHTN
crisis.
Improve survival & Estimate prognosis.
Confirming the diagnosis;
History and examination
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Diet pill use; contraceptive pill; methamphetamine
use
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Onset and length of pulmonary hypertension
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Family history of pulmonary hypertension
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Prior cardiac and other surgeries
Cont”
Symptoms
 Chest pain; dyspnoea; shortness of breath;
syncope.
Physical examination
 Loud second heart sound.
 Systolic murmur of tricuspid regurgitation.
 Diastolic murmur of pulmonary insufficiency.
 Palpable second heart sound.
 Peripheral oedema & jugular venous distension
Cont”
Diagnostic evaluation of pulmonary
hypertension;
 Chest radiograph (signs of cardiomegaly and
enlarged pulmonary arteries)
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ECG (right ventricular hypertrophy and ST-T
changes)
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Echocardiogram
– – (right ventricular hypertrophy, exclude congenital heart
disease, left ventricular diastolic dysfunction, quantify right
ventricular systolic pressure)
Cont”
Cardiac catheterization with acute
vasodilator testing;
– (evaluate pulmonary artery pressure and
resistance and degree of pulmonary
reactivity).
Positive response to
vasodilators;

Decrease in the mean pulmonary artery pressure and
resistance by 20%, or greater, with a fall to near normal levels
(<40 mg Hg).
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Experience no change or an increase in their cardiac index.
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Exhibit no change or a decrease in the ratio of pulmonary
vascular resistance to systemic vascular resistance.
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Normal right atrial pressure and cardiac output.
Cont”
Liver evaluation;
– – Liver function tests with gamma glutaryl
transferase
– – Abdominal ultrasound (porto-pulmonary
hypertension)
– – Hepatitis profile
Cont”
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Complete blood count,
urinalysis
– Prothrombin
mutation 22010
Hypercoagulable
evaluation
– – DIC screen
– – Protein C
– – Factor V Leiden
– – Antithrombin III
– – Protein S
– – Anticardiolipin
IgG/IgM
– – Russel viper
venom test
Cont”
Collagen vascular workup—looking for
autoimmune disease;
– – Antinuclear antibody with profile (DNA, Smith,
RNP, SSA, SSB, centromere, SCL-70)
– – Rheumatoid factor
– – Erythrocyte sedimentation rate
– – Complement
Cont”
Lung evaluation
– Pulmonary function tests with
DLCO/bronchodilators (to exclude
obstructive/restrictive disease)
– Sleep study and pulse oximetry (degree of
hypoxia or diminished ventilatory drive)
– CT/MRI scan of chest (evaluation of
thromboembolic disease or interstitial lung
disease)
– Ventilation perfusion test
– Lung biopsy
Cont”
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Six minute walk test/cycle ergometry
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HIV test
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Thyroid function tests
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Toxicology screen
(cocaine/methamphetamine and HIV
testing)
Management strategies;
Vasodilator therapy;
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Children who respond acutely to
vasodilator testing with nitric oxide or
epoprostenol should initially be treated
with calcium channel blockers, such as
nifedipine or diltiazem.
Cont”
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Acute trial of calcium channel blocker
therapy is reserved for those patients
who are responsive to nitric oxide or
prostacyclin.
At least 60% of children with severe
pulmonary hypertension do not
respond calcium channel antagonists.
Cont”
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These drugs can cause a decrease in
cardiac output.
Consequently, increased right atrial
pressure and low cardiac output are
contraindications to acute or chronic
calcium channel blockade.
Prostacyclin;
Imbalance in the biosynthesis of
thromboxane A2 and prostacyclin &
diminished prostacyclin synthase
expression in the lung vasculature are
seen in adults with IPAH & children
with CHD.
Cont”
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Intravenous epoprostenol made the five
year survival in patients with primary
pulmonary hypertension who were not
candidates for calcium channel blocker
therapy may be higher than 80%. And is
promising in CHD.
Disadvantages of prostacyclin analogues
include :
Cont”
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Dose dependent side effects of the drug
(nausea, anorexia, jaw pain, diarrhoea,
musculoskeletal aches and pains)
Side effects due to the method of delivery.
(through a central line) thus potential
complications include clotting, haemorrhage,
cellulitis, and sepsis.
Cont”
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Abrupt cessation causing acute
deterioration and in some cases
death.( rebound PHTN )
In patients with residual shunting,
continuous prostacylin may result in
worsening cyanosis and complications
of cerebrovascular accidents.
Alternative delivery routes for
prostacyclin analogues;
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Treprostinil, a subcutaneous prostacyclin has
been tested in a multicentre international
placebo controlled randomised study and
was found to have beneficial effects.
Can cause pain and erythema around the
infusion site, thus limiting its usefulness in
young children.
Cont”
Iloprost An inhaled prostacylin analogue,
has undergone initial trials with
significant beneficial effects on
symptomatology and quality of life.
Iloprost has a half life of 20–25 minutes
and therefore 6–9 inhalations a day
are required to be clinically effective.
Cont”
Beraprost,
 An orally active prostacyclin analogue, is
fast acting and has a half life of 35–40
minutes; it has beneficial effects, which may
be attenuated with increasing length of
treatment.
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A recent study showed comparable if not
superior PAP lowering effect to N.O.
Endothelins receptor
antagonists;
Bosentan,
a dual ET receptor antagonist, which
when used in children with pulmonary
arterial hypertension related to
congenital heart disease or IPAH, it
lowered pulmonary pressure and
resistance, and was well tolerated.
CONT”
Sitaxsentan,
 An ET receptor antagonist with high oral
bioavailability, a long duration of action.

When given orally for 12 weeks it had
beneficial effects on exercise capacity and
cardiopulmonary haemodynamics in patients
with congenital heart disease.
Phosphodiesterase-5
inhibitors;
Sildenafil
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These drugs promote an increase in cGMP
levels and thus cause pulmonary
vasodilatation.
Useful in the setting of inhaled nitric oxide
therapy withdrawal, in postoperative
pulmonary hypertension, or in the presence
of pulmonary hypertension related to
chronic lung disease.
Anticoagulation;
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Required to prevent the development
of pulmonary thrombi.
Aspirin can be used instead in
children.
In adults with IPAH, use of warfarin
improves survival sgnificantly.
Others;
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Prevent nocturnal hypoxemia by home
O2 at least 15 hrs / day.
Very good nutrition to help increase
the availability of cGMP.
Conclusions;
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Early surgical or interventional
treatment remains the corner stone in
prevention of PHTN 2nd CHD.
New anti-PHTN medications have
improved the quality of life and
survival of pts. With 1ry & 2nd PHTN
Cont”
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Perhaps inoperable CHD patients due to
severe PHTN can be reversed to operable
using combined aggressive treatment
protocols.
Cost and availability of these new
medications is a serious obstacle in our part
of the world.
Specialized integrated services for PHTN
treatment are needed.