pulmonary hypertension- an overview
TRANSCRIPT
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An overview of
Pulmonary Hypertension
Sarfraz Saleemi MRCP FCCP FACPSection of pulmonary medicine
Department of medicine
King Faisal Specialist Hospital & Research CenterRiyadh, Saudi Arabia
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1891
E. Romberg, Germany, The first reported case , Autopsy -
thickening of the pulmonary artery but no heart or lung disease
1951
D.T. Dresdale. USA,39 cases – Term ‘pulmonary hypertension’
used for the first time
1967 – 1973
10-fold increase in unexplained pulmonary hypertension in
central Europe - Aminorex Fumarate, an appetite suppressant
drug
History of Pulmonary Hypertension
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Cardiac Hemodynamics
Pulmonary vascular
resistance
High capacitance
Low resistance
Systemic vascular
resistance
Relatively fixed
capacitance
High resistance
Mean PA - PAOP
Cardiac output
(12-7)/5 = 1 Wood Unit(80 resist)
Mean Ao - mean RA
Cardiac output
(95 - 5)/5 = 18 Wood Units(1440 resist)
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Hemodynamic definition of pulmonary hypertension
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VC RA RV PA PV PC
LA LV Ao
Post-Capillary PH
(PCWP>15 mmHg)
Systemic HTN
AoV Disease
Myocardial Disease
Dilated CMP-ischemic/non-isc.
Hypertrophic CMP
Restrictive/infiltrative CMPObesity and others
Atrial Myxoma
Cor Triatriatum
PV
compressionPVOD
PAH
Respiratory
Diseases
PE
Pulmonary Hypertension
MV Disease
LVEDP
Mixed PH Pre-capillary
PH
PCWP 3 Wu
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Hemodynamic Grading of Pulmonary
Hypertension
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www.saph.med.sa
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Classification of PH
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WHO Symposia
1973 - First World Symposium on Pulmonary Hypertension, Geneva, Switzerland
1998 - Second World Symposium on Pulmonary
Hypertension , Evian, France
2003 - Third World Symposium on Pulmonary Hypertension, Venice, Italy
2008 - Fourth World Symposium on PulmonaryHypertension , Dana Point, USA
http://www.google.com/imgres?imgurl=http://www.gesundheitsforum-bw.de/servlet/PB/show/1233209/WHO.jpg&imgrefurl=http://www.gesundheitsforum-bw.de/servlet/PB/menu/1241704_l2/index.html%3FROOT%3D1133583&usg=__GsCFOnZ2d7ywQqrOETKAnE0ADvE=&h=478&w=500&sz=51&hl=en&start=2&um=1&itbs=1&tbnid=irhOViIep5tAaM:&tbnh=124&tbnw=130&prev=/images%3Fq%3Dworld%2Bhealth%2Borganization%26um%3D1%26hl%3Den%26safe%3Dactive%26sa%3DN%26rlz%3D1T4RNTN_enSA326SA326%26tbs%3Disch:1
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Clinical Classification of Pulmonary Hypertension(Dana Point 2008)
1. Pulmonary arterial hypertension (PAH)
2. Pulmonary hypertension owing to left heart disease
3. Pulmonary hypertension owing to lung diseases and/orhypoxia
4. Chronic thromboembolic pulmonary hypertension (CTEPH)
5. Pulmonary hypertension with unclear multifactorial
mechanisms
Simonneau G, Robbins IM, Beghetti M, et al. J Am Coll Cardiol. 2009 S43-S54.
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Updated clinical classification of pulmonary
hypertension (Dana Point, 2008)
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Epidemiology of PH
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PAH: how common is it?
PAH is rareEstimated prevalence of 30 50 cases per millionMean age of diagnosis 36 years
Females twice as common as males
The prevalence in certain at-risk groups is higher
• HIV-infected patients (0.50%)
• sickle cell disease (20 40%) • systemic sclerosis (30%)
True prevalence may be higher
• Peacock AJ. BMJ 2003
• Gaine SP et al. Lancet 1998
• Sitbon O et al . Am J Resp Crit Care Med 2008• Lin EE et al . Curr Hematol Rep 2005
• McGoon M et al. Chest 2004
Epidemiology of PHT
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Epidemiology of PHT
Retrospective 91-99
Prospective 99-04
SWISS MED WKLY 20 08;138(25 –26):379 –384
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At-Risk Populations for PAH
Populations Prevalence/Incidence
IPAH 1-2/million
CTD
Systemic Sclerosis
CREST syndrome30%
50%
CHDUp to 50% of patients with large VSDs develop
Eisenmenger syndrome, often associated with PAH
HIV 0.5/%
SCD 20-40%
Drugs/ToxinsDirect relationship with anorexigens (amphetamines,
cocaine); L-tryptophan may also be associated with PAH
Rich et al. CHEST 1989; Braunwald et al. Heart Disease, 6t ed.; Wigley et al. Arth Rheum 2005
Simmoneau et al. JACC 2004; 5Speich et al. CHEST 1991; Lin et al. Curr Hematol Rep 2005. Rich et al. CHEST 2000.
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Updated risk level of drugs and toxins known
to induce PAH
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Survival in IPAH
Felker et al. N Engl J Med 2000
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WHO classification of functional status of patients
with pulmonary hypertension
I No limitation of usual physical activity; ordinary physicalactivity does not cause dyspnea, fatigue, chest pain, or pre-
syncope
II Mild limitation of physical activity; no discomfort at rest; butnormal activity causes increased dyspnea, fatigue, chest pain,
or pre-syncope
III Marked limitation of activity; no discomfort at rest but lessthan normal physical activity causes increased dyspnea,
fatigue, chest pain, or pre-syncope
IV Unable to perform physical activity at rest; may have signs ofRV failure; symptoms increased by almost any physical activity
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Survival in PAH
McLaughlin VV et al. CHEST 2004
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Survival
SWISS MED WKLY 20 08;138(25 –26):379 –384
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Pathophysiology of PH
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Vascular
RemodelingOther Risk
Factors
Altered Pathwaysand Mediators
Genetic
Predisposition
Pathophysiology of PAH
Proliferation
Vasoconstriction
Thrombosis
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Humbert M et al. N Engl J Med. 2004;351:1425-1436.
Targets for Current or Emerging Therapies
Big Endothelin
Endothelin-converting
Enzyme
EndothelinReceptor A
EndothelinReceptor B
Vasoconstrictionand
Proliferation
EndothelinReceptor
Antagonists
Endothelin-1
Endothelin PathwayArginine
Nitric OxideSynthase
Vasodilatationand
Antiproliferation
Nitric Oxide
cGMP ExogenousNitric Oxide
Phosphodiesterase Type-5
PhosphodiesteraseType-5 Inhibitors
Nitric Oxide Pathway
Arachidonic Acid
ProstacyclinSynthase
Vasodilatationand
Antiproliferation
Prostacyclin
cAMP
ProstacyclinDerivatives
ProstacyclinDerivatives
Prostacyclin Pathway
Pathophysiology of PAH
B l b i i d
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Balance between vasoconstriction and
vasodilator pathway
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Prostacyclin
Prostacyclin synthase
Nitric oxide
Nitric oxide synthase
VIP
K channel
Fibrinolysis
Endothelin-1
Serotonin
Thromboxane A2
Clotting Factors
Angiopoietin-1
PAI-1
Growth factors
Oxidant stress
Inflammation
Reduced ActivityIncreased Activity
Mediators and Pathways in PAH
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Schematic Progression of PAH
Time
PAP
PVR
CO
Pre-symptomatic/Compensated
Symptomatic/Decompensating
Symptom Threshold
Right Heart
Dysfunction
Declining/Decompensated
PVR=
PAP-PCW
CO
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Diagnosis
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Symptoms
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Physical Findings
clear lungs central and peripheral cyanosis
stigmata of secondary causes of PAH:scleroderma, cirrhosis, HIV, OSA/OHS
Accentuated P2 Right ventricular S4
RV heave
Large A waves from stiff RV
Large V waves from TR
Elevated JVP Graham-Steele murmur of PR
Right ventricular S3
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Diagnostic algorithm
European Heart Journal (2009) 30, 2493 –2537
Diagnostic algorithm
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Diagnostic algorithm.
European Heart Journal (2009) 30, 2493 –2537
Diagnostic algorithm
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Diagnostic Tests
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Management
General measures
O2. Diuretics, Digoxin, anticoagulation
Specific treatment
Prostanoids, PDE5 inhibitors, EndothelinReceptor Antagonists
Non-pharmacological treatment
Atrial SeptostomyLung or Lung/heart transplant
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Conclusion
Pulmonary Arterial Hypertension is a seriousillness with poor prognosis if left untreated.
It is under-diagnosed and under-estimated
Every effort should be made to make an earlydiagnosis
Comprehensive history and physical is foundationfor diagnosis
Referral to a specialist center is mandatory in viewof specialized investigations and uniquemanagement of this illness
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THANKS