This document outlines an introduction to pulmonary hypertension including its epidemiology, etiology, pathogenesis, clinical features, treatment, and future directions. It defines pulmonary hypertension and notes the most common causes are lung diseases like COPD. In Nigeria, common causes include COPD, tuberculosis, connective tissue diseases, and sickle cell disease. The pathogenesis involves remodeling of the pulmonary vasculature from factors like endothelial dysfunction and an imbalance of vasoconstrictors and vasodilators. Over time, this can lead to right heart failure if the right ventricle can no longer compensate for the increased resistance.

1. Akinlade O. Mathias
Cardiology Unit,
LAUTECH Teaching Hospital, Ogbomoso.

2. OUTLINE
 INTRODUCTION
 EPIDEMIOLOGY
 AETIOLOGY
 PATHOGENESIS
 CLINICAL FEATURES
 TREATMENT
 COMPLICATIONS
 FUTURE DIRECTIONS
 CONCLUSION

3.  Pulmonary hypertension (PH) is a haemodynamic
and pathophysiological condition defined as an
increase in mean pulmonary arterial pressure
(PAP)greater than or equal to 25 mmHg at rest as
assessed by right heart catheterization.
 Greater than 30 mm Hg during exercise.

4.  The definition of PH on exercise as a mean PAP >30
mmHg as assessed by right heart catheterization is not
supported by published data.
 Pulmonary arterial hypertension (PAH) is a clinical
condition characterized by the presence of pre-
capillary PH in the absence of other causes of pre-
capillary PH such as PH due to lung diseases, chronic
thromboembolic PH, or other rare diseases

5. Potential sites to induce
Pulmonary Hypertension
Post-capillary
Pre-capillary

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● CO = cardiac output;
● PAP =pulmonary arterial pressure;
● PH = pulmonary hypertension;
● PWP = pulmonary wedge pressure;
● TPG = transpulmonary pressure gradient (mean
PAP – mean PWP).

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History
● First reported case: 1891
– Dr. Romberg in Germany published a description of
an autopsy case in which significant thickening of
the pulmonary artery was noted in the absence of
clearly evident cardiac or lung disease.
● Formally named: 1951
– Dr. Dresdale reported on 39 cases in United States

9. EPIDEMIOLOGY
 In adults, the most common cause of pulmonary
hypertension is lung disease, especially chronic
obstructive pulmonary disease (COPD).
 An estimated 30,000 persons die each year of
COPD, many of whom have pulmonary
hypertension and resulting right ventricular
failure as a contributing cause of death.

10.  Idiopathic pulmonary arterial hypertension
(IPAH), formerly referred to as primary
pulmonary hypertension is uncommon, with an
estimated incidence of two cases per million.
 There is a strong female predominance,
 Most patients presenting in the fourth and fifth
decades, although the age range is from infancy to
>60 years.
 1 to 2% of patients with portal hypertension or
human immunodeficiency virus (HIV) infection
have pulmonary arterial hypertension.

11.  The incidence of pulmonary arterial
hypertension in patients with collagen
vascular disease ranges from 2 to 35% in
patients with scleroderma and may reach 50%
in patients with limited scleroderma.
 Pulmonary arterial hypertension has been
reported to occur in 23 to 53% of patients with
mixed connective tissue diseases and in 1 to
14% of cases of systemic lupus erythematosus

12.  In Nigeria,
 Pulmonary hypertension-related heart disease
accounts for 0.6-28% of heart diseases,
 1.4-10.1% of echo registries,
 0.9-17% of autopsy/mortality studies.
There is no population-based study on the prevalence
of pulmonary hypertension in the country.

13.  The common causes of pulmonary
hypertension/pulmonary heart disease includes the
following: chronic obstructive airway disease, pulmonary
tuberculosis, chronic suppurative lung disease, connective
tissue disease, and sickle cell disease.
 [Others include pulmonary atherosclerosis, kyphoscoliotic
heart disease, pulmonary fibrosis, schistosomiasis, and
primary pulmonary hypertension.
Mortality associated with the disease is high. Over 70% die
in less than 6 months after the onset of symptom
 (Ogah OS. Pulmonary hypertension in Nigeria. PVRI Review
2010;2:95)

14.  So Ike et al in UNTH Enugu using Echocardiography
reported that :
 Pulmonary arterial hypertension was noted in only
three out of the fifty six sickle cell patients recruited
representing 5% of the study population.
 Pulmonary arterial hypertension appears to be
uncommon in Nigerian adults with sickle cell anaemia
in stable state.
 Journal of College of Medicine -- Vol 14, No 1 (2009)

15.  Akintunde AA reported an 86year old woman with
cortriatum with pulmonary hypertension (WHO
group 2) during preoperative evaluation.
 Akintunde AA ,Singapore Med J. 2011 Oct;52(10):e203-5

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20.  B. Demographic and medical conditions
 1. Definite
 Gender
 2 Possible
 Pregnancy
 Systemic hypertension

21.  3. Unlikely
 Obesity
 C. Diseases
 1. Definite
 HIV infection
 2. Very likely
 Portal hypertension/liver disease
 Collagen vascular diseases
 Congenital systemic-pulmonary-cardiac shunts
 3. Possible
 Thyroid disorders

22. RISK FOR PULMONARY VASCULAR DISEASE IN
PERSONS WITH CONGENITAL HEART DISEASE
Lesion % Total No. No. at Risk
Ventricular septal defect 30 9,000 3,000
Patent ductus arteriosus 9 2,700 900
Atrial septal defect 7 2,100 700
Atrioventricular septal defect 3 900 800
Aortic stenosis 5 1,500 0
Pulmonic stenosis 7 2,100 0
Pulmonic stenosis 7 2,100 0
Coarctation 6 1,800 0
Tetralogy of Fallot 5 1,500 200
Transposition of the great arteries 5 1,500 500

23. Lesion % Total No. No. at Risk
Truncus arteriosus 1 300 300
Hypoplastic right heart 2 600 50
Hypoplastic left heart 1 300 0
Double-outlet right ventricle 0.2 60 60
Total anomalous pulmonary venous
connection
1 300 300
Univentricular heart 0.3 90 90
Miscellaneous 17.5 5,250 2,625
Total 100.0 30,000 9,525 (32%)

24. Pulmonary circulation
 Low resistance, high compliance vascular bed
 Only organ to receive entire cardiac output (CO)
 Changes in CO as well as pleural/alveolar pressure
affect pulmonary blood flow
 Different reactions compared to the systemic
circulation
 Normally in a state of mild vasodilation

25. Vascular Pressure in Systemic and
Pulmonary Circulations (mm Hg)
Pulmonary
Circulation
Systemic
Circulation Arteries Arteries
Veins Veins
120/80, mean 93 25/8, mean 14
Left
Atrium
Mean 5
Right
Atrium
Mean >6
Right
Ventricle
25/2-5
Left
Ventricle
120/5-10
Lung
Body
SVR= 17.6
PVR= 1.8

26. Normally, pulmonary blood flow occurs in a low pressure,
high compliance system
 High blood pressure in the lungs
 The walls of the pulmonary arteries constrict
 The heart has to work harder to pump blood to the lungs
“High resistance and low capacity”

27. What defines Vascular Resistance?
 Ohm’s Law:
 Voltage (V) = Current (I) x Resistance (R)
 Pressure (P) = Flow (Q) x Resistance (R)
 Only at flows > 4x resting flow or pressures > 2x nml does Ohm’s law
predict changes in total pulmonary resistance
 Because of recruitment, PVR decreases with increased pulmonary arterial
pressure or flow.

28. Pathophysiology
Pulmonary vasomotor tone controlled by:
 Vasoconstrictors
 Thromboxane
 ET-1
 Leukotrienes
 Platelet activating factor
 Vasodilators
 NO
 PGI2

29. Pathogenesis
 BMPR2 abnormal: vascular hyperplasia and
abnormal neovascularization.
 Three key pathogeneses:
• Relative decrease in bioavailability of NO
• Relative increase in serum endothelin-1
• Relative deficieny of PGI2/excess of thromboxane A2 
platelet dysfxn
 Intense vasoconstriction: abnormal ATP-sensitive
K-channels.
 Immune dysfunction: autoimmune etiology in
some cases

30.  Abnormalities in molecular pathways regulating the
pulmonary vascular endothelial and smooth-muscle cells
have been described as underlying PAH.
 These include
 (I) inhibition of the voltage-regulated potassium channel,
 (II) mutations in the bone morphogenetic protein-2
receptor,
 (III) increased serotonin uptake in the smooth-muscle
cells,
 (iv) increased angiopoietin expression in the smooth-
muscle cells
 (v)and excessive thrombin deposition related to a
procoagulant state.

33.  Vasoconstrictors
:stimulate the growth of smooth muscle
: elaboration of matrix.
Endothelial injury
:release of chemotactic agents
: migration of smooth muscle cells into the
vascular wall.

34.  Remodeling of the pulmonary vascular bed
 Intimal and medial hypertrophy with proliferation of
smooth muscle cells and eventual obliteration
 Pulmonary arteries constrict
 Right heart must pump against resistance
 Right heart becomes dilated and less efficient  TR
 Less blood gets out to the lungs and to the body
 Adaptation to stress, increased activity or growth become
impossible

35. Heath-Edwards Classification
 I – Medial hypertrophy
 II – Intimal hyperplasia
 III – Occlusive changes (by fibroelastic tissue)
 IV – Dilation, medial thinning, occlusion
 V – Plexiform lesions
 VI – Necrotizing arteritis

36.  The normal pulmonary vascular bed has a
remarkable capacity to dilate and recruit unused
vasculature to accommodate increases in blood
flow.
 In pulmonary hypertension, however, this
capacity is lost, and pulmonary artery pressure is
increased at rest and further elevated during
exercise

37. PATHOGENESIS contd
 The right ventricle responds to an increase in resistance
within the pulmonary circulation by increasing RV systolic
pressure as necessary to preserve cardiac output.
 chronic changes occur in the pulmonary circulation that
result in progressive remodeling of the vasculature, which
can sustain or promote pulmonary hypertension even if the
initiating factor is removed.
 The ability of the RV to adapt to increased vascular
resistance is influenced by several factors, including age
and the rapidity of the development of pulmonary
hypertension.

38.  Coexisting hypoxemia can impair the ability of the
ventricle to compensate.
 Several studies support the concept that RV failure
occurs in pulmonary hypertension when the RV
myocardium becomes ischemic due to excessive
demands and inadequate right ventricular coronary
blood flow to the RV.
 The onset of clinical RV failure, usually manifest by
peripheral edema, is associated with a poor outcome

39. “honeymoon period”
The existence of a “honeymoon period”
during which time pulmonary
hypertension is present but the subject
exhibits few symptoms, if any. It is
during this time that compensatory
hypertrophy of the right ventricle
occurs in an effort to maintain cardiac
output in the presence of increased
pulmonary vascular resistance (PVR).

40. CLINICAL FEATURES
 fatigue and vague chest discomfort. : These
symptoms are often ignored unless the patient
has another underlying condition .
 cyanosis,
 dyspnea on exertion,
 hemoptysis,
 atypical chest pain or angina pectoris,
 syncope

41.  Dyspnea: the most common symptom of
idiopathic pulmonary arterial hypertension, is
also the most frequent symptom of the
Eisenmenger syndrome.
 Angina, a common symptom that is often
underappreciated.
 Edema

42.  o/e
 central cyanosis,
 clubbing of the digits,
 right ventricular lift,
 a palpable P2,
 increased intensity of P2 (frequently with a single
loud second heart sound),
 a pulmonic ejection sound associated with a dilated
pulmonary trunk, and
 a diastolic murmur of pulmonary insufficiency . In
the presence of heart failure, edema, ascites, and
hepatosplenomegaly develop

43. WHO Classification of Severity
 Class I: No limitation of usual physical activity; Activity
doesn’t cause dyspnea, fatigue, chest pain, or presyncope
 Class II: Mild limitation of physical activity; no discomfort at
rest; but activity causes dyspnea, fatigue, chest pain
 Class III: Marked limitation of activity; no discomfort at rest
but less than normal physical activity causes increased
dyspnea, fatigue, chest pain, or presyncope
 Class IV: Unable to perform physical activity at rest; may have
signs of RV failure; symptoms increased by almost any
physical activity

44. INVESTIGATION
 CXR
The chest radiograph demonstrates a
large right ventricle,
dilated hilar pulmonary arteries,
variably oligemic peripheral lung fields,
depending on the amount of pulmonary blood
flow

45. PH - Radiographic studies
 CXR:
-large proximal PA with peripheral
tapering (pruning)
-cardiomegaly due to enlarged RA, RV
-pleural effusion is uncommon
 CT:
-PA >aorta
-cardiomegaly, enlarged RV
-pericardial effusion

46. CXR in PAH

47. CXR in Eisenmenger Syndrome

48. Mitral Stenosis

49. PA
A
Enlarged main PA on CT
Standard view Coronal view

51.  ECG
the ECG may be unremarkable,
shows right axis deviation
right ventricular hypertrophy
secondary T wave changes;

53.  Echocardiography
The classic echocardiographic appearance of a
patient with idiopathic pulmonary arterial
hypertension shows
(i) right ventricular and
(ii) right atrial enlargement
(iii)normal or reduced left ventricular size .

55. Diagnostic testing:
Trans-thoracic echocardiography
RA LA
LV
RV
Echo transducer
PASP = (4 x [TRV]2) + RAP
CP900234-1
Echocardiography
uses Doppler
ultrasound to
estimate the
pulmonary artery
systolic pressure

56.  Transesophageal echocardiography can provide a
more precise assessment of intracardiac defects,
including detection of a patent foramen ovale.
 Saline contrast echocardiography can also be used
to assess the integrity of the atrial septum.

57.  V/Q scan ; diffuse defects of a nonsegmental nature
can often be seen in long-standing pulmonary
hypertension in the absence of thromboemboli.
 Pulmonary function tests are helpful in documenting
underlying obstructive airways disease.
 High-resolution chest CT is preferred to diagnose
restrictive lung

58.  Antinuclear antibody and
 HIV testing.
 Thyroid-stimulating hormone level be determined
periodically cos of idiopathic pulmonary hypertension.

59. Cardiac catheterization
This procedure is mandatory for accurate :
 measurement of pulmonary artery pressure,
 cardiac output,
 LV filling pressure,
 Exclusion of an underlying cardiac shunt.
 Care should be taken to measure pressures only at end
expiration

60. Pulmonary hypertension diagnosis via right heart
catheterization
From Mayo Clinic Right Heart Catheterization Training Manual – Cardiology Rotation

61. Cath Lab Testing
 Pulmonary resistance = (PAPmean - LAmean)/ CI
 expressed as Woods Units and is indexed to BSA
 Normal < 2, “inoperable” >6
 Vasoreactivity testing
 NO, Flolan, Adenosine—drop in mPAP by 10 mmHg to value < 40 mmHg
 Predicts CCB response
 Flolan testing for aortic pressure sensitivity
 100% O2 helpful in evaluating lung function
 Evaluate for septal defects
 Shed light on the issue of diastolic dysfunction
 Interpret data in context of patient’s volume status

62.  Exercise testing
useful for the initial assessment of functional
capacity before initiating treatment, as well as
serially to assess the response to therapy.
 An assessment for sleep-disordered breathing .

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Goals of Therapy
● Alleviate symptoms and improve quality of
life (exercise tolerance)
● Improve cardiopulmonary hemodynamics
and prevent right heart failure
● Delay time to clinical worsening
● Reduce morbidity and mortality
“It is not possible to vasodilate vessels that do
not exist”

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85. Targets for Therapy
Humbert et al. New Engl J Med 2004

86. The Role of CCBs
 Primary PHTN
 Treatment with CCBs in those who respond to
acute testing associated with improved 5 yr
survival (97% vs 29% non-responding, non-
treated patients).
(Rich, et al, 1992; Barst, 1999)
 + responses in 10-25% include decreased PAP &
PVR, and increased CI.
 - responses include increased CHF, decreased
CI, and death.

87.  Vasoactive medications
 Prostacyclins
 Epoprostenol (synthetic prostacyclin (PGI2) aka Flolan®)
 Treprostinil (Remodulin®), Iloprost (Ilomedin®, Ventavis®)
 Endothelin receptor antagonists
 Bosentan (Tracleer®), Sitaxsentan (Thelin®), Ambrisentan
(Letairis®)
 Phosphodiesterase type 5 inhibitors
 Sildenafil (Revatio®), Tadalafil (Cialis®)

88. RCTs of Approved Agents
Class of Drug Study/
Drug
N
Etiol
Class*
Design PositiveResults Dis-advantages
ET-1
Antagonist
BREATHE-1
Oral Bosentan/
placebo
213
PAH
III,IV
Double-
Blind
16-wk
6 MWD
Symptoms
Clinical
Worsening
CPH
Hepatic toxicity (11%;
transient, reversible)
PDE-5 Inhibitor SUPER
Sildenafil Citrate
(20, 40 or 80 mg tid)
278
IPAH,CT
CHD
II, III
Double-
blind,
placebo
12 wks
6 MWD
CPH
Symptoms
Headache, flushing,
dyspepsia
Prostacyclin
analogue
Inhalational
Iloprost/
Placebo
203
PH
III-IV
Double-
blind
12-week
Composite
Endpoint
6 MWD, sx
Administration
6 to 9 times daily
Prostacyclin
analogue
SQ Treprostinil/
SQ placebo
470
PAH
II-IV
Double-
blind
12-wk
6 MWD
Symptoms
CPH
Pain, erythema
at infusion site
Side effects
Prostacyclin IV Epoprostenol/
Conventional Rx
81
PPH
III,IV
Open-
Label
12-wk
6 MWD
Symptoms
CPH
Survival
Indwelling central line
Pump
(infection,malf)
Side effects

90. cGMP Pathway

91. Sildenafil
 Sildenafil citrate is a selective and potent inhibitor of
cGMP-specific phosphodiesterase type 5 (PDE 5)
 PDE5 is the major subtype in the pulmonary vasculature
and is more abundant in the lung than in other tissues
 Pulmonary vascular cGMP levels can be ↑ by inhibiting
phosphodiesterases responsible for cGMP hydrolysis
 Relatively selective pulmonary vasodilation with little
systemic hypotension
 Recommended for WHO Class II and III

92. Sildenafil
 In animal models of acute pulmonary hypertension
sildenafil decreased pulmonary artery pressures in a
dose-dependent manner
 Several case reports now exist suggesting sildenafil is
effective

93. Sildenafil Trial
Galie, N, et al. Sildenafil Citrate Therapy for PAH. NEJM 2005;353:2148-57.

94. Sildenafil Trial

95. Sildenafil
FDA approved dose is 20 mg tid
Higher doses often used given hemodynamic findings

96. Sildenafil – Adverse Effects
 Abdominal pain, nausea, diarrhea
 Hypotension, vasodilation, hot flushes
 Dry mouth, arthralgia, myalgia
 HA, abnormal dreams, vertigo
 Dyspnea, abnormal vision, deafness
 Penile erection, UTI, vaginal hemorrhage
 Retinitis of prematurity ………

98. Endothelin
Clozel. Ann Med. 2003

99. Endothelin is increased in IPAH and PAH associated with
other Diseases

100. Bosentan
 Specific and competitive antagonist at endothelin
receptor types ETA and ETB
 Blocks the action of ET-1, a neurohormone with potent
vasoconstrictor activity in the endothelium and
vascular smooth muscle
 FDA approved 11/2001

101. Study 351 - Bosentan
Channick R, et al. Effects of the dual endothelin-receptor antagonist
bosentan in patients with pulmonary hypertension: a randomised
placebo-controlled study. Lancet 2001;358:1119-23

102. BREATHE 1 Trial - Bosentan
Rubin LJ, et al. The New England Journal of Medicine; 2002; 346(12):896-
903

103. BREATHE 1 – 6min Walk Test
62.5 mg bid 125 or 250 mg bid
-40
-20
0
20
40
60 Bosentan (n = 144)
Placebo (n = 69)
Baseline Week 4 Week 8 Week 16
P = 0.0002

Walk
Distance
(meters)
Mean ± SEM

104. BREATHE 1 – Time to Clinical
Worsening

105. BREATHE-3 – Bosentan in Kids
 Inclusion Criteria
 Age: 2–17 yrs, WHO class II–III
 PPH or CHD
 Oxygen sats > 88%
 Concomitant epoprostenol (Flolan®) (at least 3
months)
 Exclusion Criteria
 Liver Disease (ALT/AST > 2 X ULN)
 Poor Cardiac Fxn (CI < 2 l/min /m2 )
 Low BP (Systolic < 80 mm Hg)
Dunbar Ivy, UCHS

106. BREATHE-3 - Conclusions
 Significant hemodynamic improvements were
observed after 12 weeks of bosentan
 Bosentan was well tolerated in children with PAH,
either alone or in combination with epoprostenol

107. Bosentan – Who Qualifies?
 Indication: Treatment of pulmonary arterial
hypertension in patients with WHO Class III or IV
symptoms, to improve exercise ability and decrease the
rate of clinical worsening

108. Bosentan – Lab Monitoring
Liver function testing
 Prior to initiation of treatment and monthly
 ↑ in ALT, AST or bilirubin. Dose-dependent,
typically asymptomatic, and reversible after
treatment cessation
 Hemoglobin
 Prior to initiation of treatment
 After 1 month, then every 3 months
 HCG
 Prior to initiation of treatment and monthly (teratogen)

109. Bosentan – Adverse Effects
 Cardiovascular: edema (lower limb), flushing,
hypotension, palpitations
 CNS: fatigue, headache
 Dermatologic: pruritus
 GI: dyspepsia
 Hematologic: decrease in H/H
 Respiratory: nasopharyngitis
~$40,000 per year

111. Prostacyclins
 Promote vasodilation
 Inhibit platelet aggregation
 Inhibit vascular smooth muscle proliferation
 On treatment algorithm for WHO Class III or IV
 Only Flolan and Remodulin approved in US

112. Epoprostenol (Flolan )
 Actions: relatively locally acting vasodilatation
and platelet inhibition
 Most potent effect -- cardiac output in
patients with PAH
 Resting HR, mean right atrial pressure, and
a marked improvementin survival
 t½ = 3-5 mins
 Abrupt cessation can be fatal
 May worsen intrapulmonary shunt initially
 Contraindicated in veno-occlusive disease

113. Epoprostenol
 Adverse effects 2˚ delivery system
 Pump malfunction
 Catheter related infections
 Thrombosis
 Drug-induced side effects
 Flushing, HA, dizziness, anxiety, hypotension, chest pain
 N/V, abd pain, diarrhea
 Myalgias, arthralgias, jaw pain, cramps, dyspnea
 Thrombocytopenia, rash
 Tolerance
 Unstable (Reconstituted daily in alkaline buffer and refrigerated)
 Cost
 Outpatient cost up to $100,000 per year (adult)

114. Epoprostenol

115. Epoprostenol
Improved exercise capacity and hemodynamics
Sitbon, O et al. J Am Cardiol 2002;40:780-88

116. Epoprostenol/Treprostinil Pump

117. Treprostinil (Remodulin)
 IV or SQ administration
 Longer half-life than epoprostenol (4 hrs)
 Pre-mixed
 Stable at room temperature
BUT
 Need to change site /pump q3 days
 Site pain major problem

118. SQ Remodulin
6 minute walk distance compared
Simonneau G. et al. Am J Resp Crit Care Med 2002;165:800-804.

119. Iloprost (Ventavis®)Inhalation
Solution
 Indicated for inhalation via the Prodose® AAD® system only
 2.5 mcg initial dose
 increase to 5 mcg if 2.5 mcg dose is tolerated
 maintain at maximum tolerable dose (2.5 mcg or 5 mcg)
 6-9 inhalations daily during waking hours; 8-10 minutes each
Properties:
 Exerts preferential vasodilation in well- ventilated lung regions
 Longer duration of vasodilation than PGI2 (t ½ = 40 min)

120. Inhalational Iloprost
Olschewski et al, NEJM 2002, 347:322-9

121. Outcomes
 Some improve
 PPHN
 Lung dx—as the dx improves, so does the PHTN
 In the absence of a correctable anatomic lesion, reports of spontaneous
remission are very rare
 Some die rapidly
 Pulmonary veno-occlusive disease and CHD leading to cardiovascular
collapse within one year
 Alveolar capillary dysplasia
 Congenital pulmonary vein stenosis
 Some get worse slowly
 Seems to be most common and may need lung transplant
 Must stay on top of associated OSA, RAD, chronic aspiration and other
triggers

122. Interventional therapy
 (i) Surgical Repair for Congenital Heart Disease.
 (ii) Atrial Septostomy
 The rationale for the creation of an atrial
septostomy in patients with pulmonary arterial
hypertension is based on experimental and
clinical observations suggesting that an
interatrial defect allowing right-to-left shunting
may be beneficial in the setting of severe
pulmonary arterial hypertension

123. Who is a Candidate for Lung Tx?
 PHTN associated with rapid death
 All previous medical therapy has failed, and
the probability of survival for another 2 yrs
predicted to be <50%.
 Nutritional and psychological issues important
 Time to listing is a function of:
 Predicted duration of survival
 Predicted waiting time on transplant list
 Survival rates: 1 yr = 65-70%, 5 yr = 40-50%

124. Outcome of Children with PHN
referred for Lung Tx
 8/24 children with PHN referred for LTX died prior
to transplant
 Retrospective application of predictive score (RA x
PVR) showed that death prior to tx was predictable
(p<0.009)
 1/3 of children with PHN are referred for LTX too
late to be expected to survive until organs become
available.
Bridges, et al., 1996

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126. www.escardio.org/guidelines

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128. www.escardio.org/guidelines

129. www.escardio.org/guidelines

130. www.escardio.org/guidelines

131. www.escardio.org/guidelines

132. www.escardio.org/guidelines

133. www.escardio.org/guidelines

134. www.escardio.org/guidelines

135. Looking to the Future
 Better therapies and prevention require a better
understanding of the mechanisms which trigger and
perpetuate PHN:
 The genetic basis of the disease
 The role of proliferation and neovascularization.
 Better delivery methods for better drugs.

136. Future Directions
 Future progress is likely to focus on attempts
 to discover final common pathways for
pulmonary hypertensive diseases,
 to develop molecular and physiologic tests to
monitor and diagnose pulmonary vascular
disease, and
 to test currently available therapies and
 develop new ones based on established
pathobiologic mechanisms.

137. Summary
 Pulmonary arterial hypertension is a progressive disease
with significant morbidity and mortality
 Right heart failure is an important development which
clearly prognosticates and marks disease progression
 Treatment of right heart failure is essential
 Therapies with proven benefit in transpulmonary
hemodynamics, functional class and exercise tolerance
include ET-1 receptor antagonism (bosentan), prostanoids,
and oral sildenafil.
 Continuous IV Flolan is reserved for advanced (class IV)
disease where there is a proven survival benefit

138. THANK
YOU
Ese o
Obulu o
merci

139. REFERENCES
 Cecil’s Medicine 23rd Edition
 Harrison’s Principle of Medicine
 Kumar and Clark’s Clinical Medicine
 European Society of Cardiologists , Guideline for the
diagnosis and treatment of pulmonary hypertension
(European Heart Journal (2009) 30, 2493–2537)

140.  AMERICAN HEART ASSOCIATION SCIENTIFIC
STATEMENT
Circulation June 14, 2005 vol. 111 no. 23 3167-3184 .
 Medscape Reference, Infective Endocarditis
John L Brusch, MD, FACP; Chief Editor: Burke A
Cunha, MD