Pulmonary Hypertension- An overview

8/13/2019 Pulmonary Hypertension- An overview

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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



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Diagnostic algorithm.

European Heart Journal (2009) 30, 2493 –2537



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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

Documents

Pulmonary Hypertension- An overview