Out-patient Management of Pulmonary Hypertension

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Out-patient Management of Pulmonary Hypertension

• Jameel A. Al-Ata, MD
• KAAUH KFSHRC-JED.

Taif 14th annual cardiovascular conference ,
march 2006.
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Content

• Management Strategies
• Conclusion.

• Definition Types
• Epidemiology
• Pathophysiology
• PHTN CHD
• Concepts Goals of management
• Workup

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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.

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WHO classification 1998

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Pulmonary arterial hypertension

• 1.1 Idiopathic pulmonary hypertension
• 1.2 Familial

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Cont

• 1.3 Associated with
• Collagen vascular disease
• Congenital systemic to pulmonary shunts
• Portal hypertension
• HIV infection
• Drugs (anorexigens)/toxins
• Other thyroid disorders Gaucher disease,
  hereditary haemorrhagic telangiectasia,
  haemoglobinopathies

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Cont

• 1.4 Persistent pulmonary hypertension of the
  newborn
• 1.5 Pulmonary veno-occlusive disease

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Pulmonary hypertension with left heart disease

• 2.1 Left sided atrial or ventricular heart
  disease
• 2.2 Left sided valvular disease

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Pulmonary hypertension associated with disorders
of the respiratory system and/or hypoxaemia

• 3.1 Chronic obstructive pulmonary disease
• 3.2 Interstitial lung disease
• 3.3 Sleep disordered breathing

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Cont

• 3.4 Alveolar hypoventilation disorders
• 3.5 Chronic exposure to high altitude
• 3.6 Neonatal lung disease
• 3.7 Alveolar-capillary dysplasia
• 3.8 Other

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Pulmonary hypertension due to chronic thrombotic
and/or embolic disease

• 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.

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Miscellaneous,

• e.g. Sarcoidosis

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Genetics Epidemiology

• 6 of primary pulmonary hypertension cases are
  familial.
• The disease is inherited as an autosomal dominant
  with incomplete penetrance.
• 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.

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CONT

• 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.

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Cont

• 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.

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Cont

• 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.

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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 ).

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Cont

• 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,

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Cont

• Lung hypoplasia.
• Lung fibrosis.
• Chronic thromboembolism.

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PHTN CHD

• 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 Downs syndrome may have an
  increased risk of pulmonary hypertension.

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Cont

• 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 left-to-right
  shunt lesions.

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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.
• Palliative shunting operations ( e.g. central
  aorto-pulmpnary shunts ) may lead to the
  development of pulmonary hypertension.

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Eisenmenger syndrome

• 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.

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Cont

• 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.

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Concepts Goals of management

• 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).

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Cont

• Monitor response to therapy.
• Reverse back to an operable state.
• Reduce the post operative risk of PHTN crisis.
• Improve survival Estimate prognosis.

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Confirming the diagnosis

• History and examination
• Diet pill use contraceptive pill
  methamphetamine use
• Onset and length of pulmonary hypertension
• Family history of pulmonary hypertension
• Prior cardiac and other surgeries

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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

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Cont

• Diagnostic evaluation of pulmonary hypertension
• Chest radiograph (signs of cardiomegaly and
  enlarged pulmonary arteries)
• ECG (right ventricular hypertrophy and ST-T
  changes)
• Echocardiogram
• (right ventricular hypertrophy, exclude
  congenital heart disease, left ventricular
  diastolic dysfunction, quantify right ventricular
  systolic pressure)

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(No Transcript)
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Cont

• Cardiac catheterization with acute vasodilator
  testing
• (evaluate pulmonary artery pressure and
  resistance and degree of pulmonary reactivity).

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Positive response to vasodilators

• Decrease in the mean pulmonary artery pressure
  and resistance by 20, or greater, with a fall to
  near normal levels (lt40 mg Hg).
• Experience no change or an increase in their
  cardiac index.
• Exhibit no change or a decrease in the ratio of
  pulmonary vascular resistance to systemic
  vascular resistance.
• Normal right atrial pressure and cardiac output.

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Cont

• Liver evaluation
• Liver function tests with gamma glutaryl
  transferase
• Abdominal ultrasound (porto-pulmonary
  hypertension)
• Hepatitis profile

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Cont

• Complete blood count, urinalysis
• Hypercoagulable evaluation
• DIC screen
• Factor V Leiden
• Antithrombin III

• Prothrombin mutation 22010
• Protein C
• Protein S
• Anticardiolipin IgG/IgM
• Russel viper venom test

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Cont

• Collagen vascular workuplooking for autoimmune
  disease
• Antinuclear antibody with profile (DNA, Smith,
  RNP, SSA, SSB, centromere, SCL-70)
• Rheumatoid factor
• Erythrocyte sedimentation rate
• Complement

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Cont

• Lung evaluation
• Pulmonary function tests with DLCO/bronchodilator
  s (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

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Cont

• Six minute walk test/cycle ergometry
• HIV test
• Thyroid function tests
• Toxicology screen (cocaine/methamphetamine and
  HIV testing)

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Management strategies

• Vasodilator therapy
• 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.

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Cont

• 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.

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Cont

• 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.

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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.

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Cont

• 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

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Cont

• 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.

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Cont

• 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.

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Alternative delivery routes for prostacyclin
analogues

• 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.

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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 2025 minutes and
  therefore 69 inhalations a day are required to
  be clinically effective.

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Cont

• Beraprost,
• An orally active prostacyclin analogue, is fast
  acting and has a half life of 3540 minutes it
  has beneficial effects, which may be attenuated
  with increasing length of treatment.
• A recent study showed comparable if not superior
  PAP lowering effect to N.O.

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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.

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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.

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Phosphodiesterase-5 inhibitorsSildenafil

• 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.

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Anticoagulation

• 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.

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Others

• Prevent nocturnal hypoxemia by home O2 at least
  15 hrs / day.
• Very good nutrition to help increase the
  availability of cGMP.

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Conclusions

• 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

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Cont

• 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.

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THANK YOU