PULMONARY HYPERTENSION

PULMONARY HYPERTENSION

INTRODUCTION

BRIEF HISTORY

WHAT IS PH?

WHAT CAUSES PH?

SIGNS AND SYMPTOMS

DIAGNOSIS OF PH

TREATMENT OF PH

INTRODUCTION

BRIEF HISTORY

WHAT IS PH?

WHAT CAUSES PH?

SIGNS AND SYMPTOMS

DIAGNOSIS OF PH

TREATMENT OF PH

INTRODUCTION

In the human body, there are two types of circulation that enable distribution of blood throughout the body.

The portion that pumps oxygenated blood from the left side of the heart via the left ventricle to all parts of the body is known as the SYSTEMIC CIRCULATION.

On the other hand, the portion that pumps deoxygenated blood from the right side of the heart via the right ventricle into the lungs to obtain oxygen is referred to as the PULMONARY CIRCULATION.

Millions of people are affected by a condition known as high blood pressure (hypertension) whereby the blood travels through the body’s arteries at a pressure higher than normal.

PULMONARY HYPERTENSION is a far less common type of high blood pressure that affects specifically the arteries in the lungs. Pressures in the lung arteries are normally significantly lower than the pressures in the systemic circulation. Pulmonary hypertension occurs when the pressure in the pulmonary circulation becomes abnormally elevated. It is a serious condition that becomes progressively worse and eventually proves fatal.

INTRODUCTION

INTRODUCTION

An estimated of 500 – 1000 new cases are diagnosed annually. There is an incidence of about 2-3 per million per year and a prevalence of 15 per million.

This disease can occur in men, women and children of all ages. However, it is most common in females between 20 and 40 years old, with twice as many cases reported in women then men.

The condition is rare in children but is sometimes seen in infants born with heart defects. Pulmonary hypertension may be a primary or secondary cause of hypoxia in neonates.

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The first reported case – 1891

• E. Romberg, German doctor

• published description of a patient who, at autopsy, showed

thickening of the pulmonary artery but no heart or lung disease

In 1951, 39 cases were reported by Dr. D.T. Dresdale in the United States. The illness received its name.

Between 1967 and 1973, a 10-fold increase in unexplained pulmonary hypertension was reported in central Europe. The rise was subsequently traced to aminorex fumarate, an amphetamine-like drug introduced in Europe in 1965 to control appetite. It was later removed from the market.

WHAT IS PULMONARY HYPERTENSION?

Ordinarily, blood vessels in the lungs provide less resistance to blood flow than blood vessels in the rest of the body do. Hence, blood pressure is usually much lower in the lungs. While pressure in general circulation is about 120/80 mm Hg, in the pulmonary arteries, it is only around 25/15 mm Hg.

Mean (average) pulmonary artery pressure

= number between highest and lowest pressures

Normal

at rest : 14 mm Hg

Pulmonary hypertension

at rest : 25 mm Hg

during exercise : 30 mm Hg

Primary Pulmonary Hypertension

• no underlying cause for the high blood pressure in lungs

• likely to begin with spasm of the muscle layer in pulmonary arteries

• patients are rather sensitive to substances that cause blood vessels

to constrict

• may have an inherited predisposition for the disease

Secondary Pulmonary Hypertension

• results directly from another medical problem

• most probable from diseases that impedes flow of blood through

lungs or that causes periods of low oxygen in blood

• eg. Chronic Obstructive Pulmonary Disease, scleroderma, sleep

apnea, pulmonary fibrosis, lung diseases such as asbestosis

ClassificationI. Classification of PH based on etiology

Classification…

Abnormally high BP in pulmonary arteries

Increased pressure damages large and small pulmonary arteries

Blood vessel walls thicken

Cannot transfer oxygen and carbon dioxide normally

Levels of oxygen in blood fall

Constriction of pulmonary arteries

Further increase in pressure in pulmonary circulation

Pulmonary Hypertension

right side of heart must work harder push blood through pulmonary arteries to lungs

right ventricle thickens and enlarges

cor pulmonale

Heart Failure

In some people, the bone marrow will produce more red blood cells to compensate for less of oxygen in blood leading Polycythemia

Extra RBCs cause the blood to become thicker and stickier, further increasing the load on the heart Pulmonary Embolism

Functional Classification

A. Class I- Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnoea or fatigue, chest pain, or near syncope.

B. Class II- patients with pulmonary hypertension resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnoea or fatigue, chest pain, or near syncope.

C. Class III- patients with pulmonary hypertension resulting in marked. Limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnoea, fatigue, and chest pain or near syncope.

D. Class IV -patients with pulmonary hypertension with inability to carry out any physical activity without symptoms. these patients manifest signs of right heart failure. Dyspnoea and /or fatigue may be present even at rest. Discomfort is increased by any physical activity

WHAT CAUSES PULMONARY

HYPERTENSION?

Although the exact cause of primary pulmonary hypertension is unknown, scientists believe that most people who develop the disorder are especially sensitive to substances that cause blood vessels to constrict.

Cocaine and fenfluramine (fen-phen), which was withdrawn from the market in 1997, are two of the substances that may contribute to PH in many people.

Other people with PH have an inherited predisposition for the disease. In these people, PH is triggered by another medical condition such as chronic liver disease (cirrhosis), AIDS, sickle cell anemia, scleroderma and lupus.

Pulmonary hypertension resulting directly from another medical problem is called secondary pulmonary hypertension. Medical conditions that may lead to secondary PH include :

blood clots in the lungs (pulmonary emboli)

chronic obstructive pulmonary disease such as emphysema

connective tissue disorders, such as scleroderma

sleep apnea – upper airway obstructed during sleep

congenital heart disease

obesity with reduced ability to breathe (Pickwickian syndrome)

neuromuscular diseases involving respiratory muscles

HIV infection

lung diseases such as pulmonary fibrosis (causes scarring in

the tissue between the lungs’ air sacs)

Left-sided heart failure

• heart’s left ventricle weakens and cannot pump out enough blood

• increase in pressure backs up through pulmonary veins to

arteries in lungs

High Altitude

• above altitude of 8000 feet - may develop PH

• low blood oxygen (hypoxemia)

• constricts small pulmonary arteries

• climb to high elevations without first becoming acclimated

• risk of pulmonary edema too – air sacs filled with fluid instead of

with air, always associated with PH

The overall rise in blood pressure in PH is the end result of a process which begins with changes in the endothelial cells that line the lungs’ arteries.

Changes → causes formation of extra tissue → blockage in vessels

Scarring (fibrosis) usually also occurs → arteries stiff and narrow

These causes increased resistance to blood flow which raises pressure in the pulmonary arteries.

Less often, PH is caused by extensive loss of lung tissue from surgery/trauma.

Injury to endothelial cells leads to overproduction of endothelin – key cause of blood vessel scarring and spasm & to reduced production of nitric oxide and prostacyclins – 2 key body chemicals which keep blood vessels relaxed and open.

The ‘Two-Hit’ Hypothesis

According to the hypothesis, vascular abnormalities characteristic of PPH are triggered by accumulation of genetic and/or environmental insults in a susceptible individual. A combination of germline BMPR2 mutation (‘first hit’) and the ingestion of appetite suppressants (‘second hit’) were used to generate the clinical disease.

A genetic cause of the familial form of primary PH has been discovered. It is caused by mutations in a gene called BMPR2, as used in the ‘Two-Hit’ Hypothesis.

BMPR2 encodes a receptor (transforming growth factor beta type II receptor) that sits on the surface of cells and binds molecules of the TGF-beta superfamily.

Binding triggers conformational changes → series of biochemical reactions

↓

affect cell’s behaviour

The mutations block this process. Hence, this discovery provides means of genetic diagnosis and a potential target for the therapy with familial and possibly, sporadic primary pulmonary hypertension.

SIGNS AND SYMPTOMS

Like other forms of high blood pressure (hypertension), the signs and symptoms of pulmonary hypertension are subtle in the early stages of the disease and may not be apparent for months or even years. As the disease progresses, these signs become more noticeable. Also, the symptoms of PH are often hidden by the underlying condition causing the disease.

Symptoms, however, tend to vary from patient to patient.

The diagnosis of PH are often overlooked by physicians. It is sufficiently common and of such high impact that all patients with scleroderma should be screened for its presence on a regular basis.

shortness of breath (dyspnea)

Initially, only short of breath when exert oneself physically but

eventually may be short of breath most of the time, even when

at rest.

fatigue or light-headed upon exertion

dizziness or fainting spells (syncope)

swelling (edema) in ankles, legs and eventually in

abdomen (ascites) – fluid leak out of veins and into tissues

bluish colour to lips and skin (cyanosis)

coughing (sometimes with blood) and wheezing

distended neck veins

enlarged liver

racing pulse or heart palpitations

angina-like chest pain

feel weak – body tissues not receiving enough oxygen

achy joints (often developed years before apparent onset of

disorder)

Signs and Symptoms in Children

The symptoms of PH for children are similar to that of an adult, though children are more likely to experience tiredness, dizziness and breathlessness and for many, fainting is common.

fail to put on weight like a normal child

slowed growth

Children tend to be diagnosed earlier than adults, but just like adults, they are often misdiagnosed several times before a correct diagnosis is made. The commonest misdiagnosis is asthma.

Untreated PH in children worsens quicker than the same condition in adults. However, with treatment, children appear to have an overall better prognosis than adults.

DIAGNOSIS OF PH

It is often very difficult to initially diagnose PH. In fact, there is often a lengthy delay between the time when patients first visit their doctor and the time they receive specialist care at a hospital.

Since there is no single test that will tell the healthcare team if a patient has PH, it is important to consider all associated diseases as well as other causes of breathlessness, such as certain lung and heart diseases and blood clots. The ruling out of different diseases that are possible causes of particular symptoms is called the differential diagnosis.

A definite diagnosis of PH usually requires passing a tube through a vein in an arm or a leg into the right side of the heart to measure the blood pressure in the right ventricle and the pulmonary artery.

For patients with suspected PH, there are several initial steps that are commonly taken to confirm the diagnosis. These are first discussed between the patient and the healthcare team :

• history of present illnesses

• past medical history

• family history

• any past or present medications that the patient may have taken

A thorough physical examination will also take place. After this, a number of tests may be ordered to aid in assessment and diagnosis of PH.

Chest X-Ray

Based on the symptoms, a doctor may suspect PH in people who have an underlying lung disorder. A chest x-ray may show that the pulmonary arteries are enlarged.

This imaging test offers the physician a picture of the general size, shape and structure of the heart and lungs. One of the things the physician will check is whether the right side of the heart is enlarged.

Echocardiography (Ultrasonic Cardiography)

This test uses sound waves to track the structure and function of the heart. It can compose images of a beating heart on a monitor and detects:

• heart’s thickness, size and function

• motion pattern and structure of the four heart valves

→ revealing any potential leakage (regurgitation)

• thickening of right ventricle, enlarged right heart

• reversal of blood through tricuspid valve

• extent of lung damage

A specific echocardiogram, Doppler ultrasound, is sometimes used to determine pulmonary artery pressure.

Exercise echocardiogram – determine how well heart works under stress

Electrocardiogram (ECG)

ECG is a record of the electrical activity produced by the heart. Abnormal rhythms (arrhythmias) may indicate that the heart or part of the heart is undergoing unusual stress.

Exercise ECG helps evaluation of performance of the heart during exercise, for example, walking on a treadmill in the examination room.

Pulmonary Angiogram

Used to measure circulation in the lungs and to visualize clots in the lung on x-rays. The test involves insertion of a thin catheter into the pulmonary artery through which an iodine dye is injected.

Image of any blood clots present in the lung can be observed and circulation of blood through lung’s blood vessels can be tracked.

Perfusion Lung Scan

Uses small amounts of radioactive tracers (radioisotopes) to study blood flow in the lungs. Radioisotopes are attached to radiopharmaceuticals which are then injected into a vein the arm. A gamma camera takes pictures of blood flow in the lungs’ blood vessels. It is generally used to determine whether blood clots may be causing symptoms of PH.

Pulmonary Function Tests

Non-invasive tests to measure how much air your lungs can hold and the airflow in and out of your lungs. They can also measure the amount of gases exchanged across the membrane between the lung wall and capillary membrane. During the tests, the patient will be asked to blow into a spirometer. An abnormality here may be amongst the first indication of PH.

Computerized Tomography (CT)

Magnetic Resonance Imaging (MRI)

Organs can be scanned in two-dimensional ‘slices’. Split-second computer processing creates images as a series of very thin x-ray beams pass through the body. A contrast medium is used to help visualization. The fast CT machine can scan arteries in less than 20 seconds as opposed to 20 minutes for a standard CT. Speed is important because it allows the dye to be visualized while still in the arteries.

Uses no x-rays but instead, a computer creates tissue ‘slices’ from data generated by a powerful magnetic field and radio waves. Although not yet routinely used to diagnose PH, it is showing great value in assessing the pulmonary arteries. It cannot, however, measure artery pressure.

Other screening or diagnostic methods

exercise testing

ventilation-perfusion (V/O) scanning

arterial blood gas studies

central hematocrit count

serum glucose and calcium levels count

platelet count

hyperoxia (100% oxygen) challenge test

TREATMENT OF PH

6 Minute walk Testing

In patients with PAH, serial determinations of functional class and exercise capacity assessed by the 6 minute walk test provide benchmarks for disease severity, response to therapy, and progression.

ACCP: QOE: good; Benefit: intermediate; SOR: A

Treatment Goals in PAH

Improved exercise capacityImproved functionImproved hemodynamicsImproved survivalPrevention of clinical worsening

No improvement or deterioration

Therapy for PAHFunctional class II / III / IV

General CareOral anticoagulants ;B for IPAH, E/C for other PAH] diuretics O2 [E/A] digoxin

Acute Vasoreactivity Testing [A for IPAH, E/C for other PAH]YES NO

Oral CCB [B for IPAH], E/B for other PAH]

Functional Class III Functional Class IV

Sustained Response

YES NO

Continue CCB

Endothelin Receptor Antagonists(Bosentan) [A]

orChronic IV Epoprostenol [A]

orProstanoid Analogues

SQ Treprostinil [B], Inh Iloprost [B], Beraprost [I]

PDE-5 Inhibitors (Sildenafil) [C]

Chronic IV Epoprostenol [A]Bosentan [B]

Treprostinil [B]Chronic IV Iloprost [C]

Atrioseptostomy Lung Transplantation

Therapy Targets for PAH

Humbert M, Sitbon O, Simonneau G. N Engl J Med 2004;351:1425-36

Targeting the Mechanism of PAH

Calcium Channel Blockers

For patients (20%) with meaningful reduction of PAP associated with reduction of PVR on acute vasoreactivity tests.

Nifedipine 240mg/day, 30 mg BIDDiltiazem 900mg/day, 60mg TIDLimiting factors for dose increase:

systemic hypotension and lower limb peripheral edema

Pathophysiology in PAH

Deficiency of prostaglandin and an excess of thromboxane in PAH patients

Christman et al, NEJM 1992

Decreased expression of prostacyclin synthase in lungs from patients with severe PAH

Tuder et al, AJRCCM 1999

Epoprostenol

PGI2

Potent vasodilator in both the pulmonary and systemic circulation

Has antiplatelet aggregatory activityExogenously administered prostanoid analoguesUnstable at acidic pH, not taken orallyVery short half life,<6 minsFor moderately severe to severe PAH

Epoprostenol

Requires constant IV administration

Kept cold prior to infusion Initial dose: 1 – 2 ng/kg/min Gradually titrating in

increments of 1- 2 ng/kg/min, based upon side effects and tolerance to reach a “plateau” between 20 – 40 ng/kg/min

Epoprostenol

Side effects: Flushing, headache, jaw pain with first bite of food, diarrhea, nausea, blotchy erythematous rash and musculoskeletal pain (legs and feet )

Chronic IV therapy: Line related infections, catheter associated venous thrombosis, thrombocytopenia

Treprostinil

Stable prostacyclin analogueHalf life of 3 hoursStable at room temperatureUndergoing research: Inhaled treprostinil

Treprostinil

Developed for SC delivery

Initially 1.25 ng/kg/min up to maximum of 22.5 ng/kg/min

Side effects: Headache, diarrhea, nausea, rash, jaw pain, infusion site pain, erythema or induration

Iloprost

Prostacyclin analogueStable at room temperature, at pH 7.4 and

normal lightSerum half-life of 20 – 25 minsFor functional class 3 – 4

Iloprost

Administered via nebulized aerosol

Administered 6 – 9 times a day, each inhalation requires 10 – 15 mins

Dose: 2.5 – 5 ug, median inhaled dose of

30 ug/daySide effects: Cough,

headache and flushing

Beraprost

First chemically stable and orally active prostacyclin analogue

Peak concentration is reached after 30 minutes and elimination half-life is 35 – 40 minutes after oral administration

Median dose of 80 ug PO dailyApproved therapy for PAH in Japan

Endothelin

A 21-amino acid peptide released primarily from A 21-amino acid peptide released primarily from the endotheliumthe endothelium

TrpTrpIleIleIleIleAspAspLeuLeuHisHisCysCysTyrTyrValVal PhePheCysCys

CysCysCysCys SerSer

GluGlu

SerSerSerSerLeuLeu

MetMet

AspAsp

LysLys

NHNH22

COCO22

Pathophysiology in PAH

Endothelin 1 is a potent vasoconstrictor and

SM mitogenIncrease in vascular tone and pulmonary

vascular hypertrophy2 distinct endothelin- receptor isoforms:

ETA – facilitates vasoconstriction and proliferation of vascular SM cells

ETB – involved in clearance of endothelin and cause vasodilatation and NO release

Expression of Endothelin in the Lungs of PH Patients

Giaid A et al. N Engl J Med. 1993 Jun 17;328(24):1732-9. Giaid A et al. N Engl J Med. 1993 Jun 17;328(24):1732-9.

Bosentan

Orally active nonpeptide antagonist of both endothelin receptor subtypes

Prevents and even reverses the development of PH, pulmonary vascular remodelling and right ventricular hypertrophy

Initial dose of 62.5 mg bid for first 4 weeks and followed by target dose of 125 mg bid

Side effects: Hepatotoxicity and teratogenicity

Sitaxsentan

Selective ETA antagonist

Has oral bioavailability and a long duration of action (t 1/2, 5-7h) .

Approximately 6,500 fold more selective as antagonist for ETA compared with ETB

receptors.Side effects: ↑ INR and prothrombin time

due to inhibition of CYP2C9 P450 enzyme

Ambrisentan

ETA selective antagonist

Under research

Phosphodiesterase Inhibitors

SildenafilPotent and highly specific PDE5 inhibitor Inhibits degradation of cGMP by

phosphodiesterases Prevent rebound pulmonary

vasoconstriction after acute withdrawal of inhaled NO

Revatio – contains sildenafil same active ingredient used in Viagra blocks the enzyme phosphodiesterase accentuates actions of nitric oxide opens blood vessels in the lungs - dilation side effect - vision problems

Anticoagulant

warfarin (Coumadin) prevent formation of blood clots within pulmonary arteries risk of bleeding complications – prevent normal blood coagulation periodic blood tests – check how well the drug is working more than 100 drugs can interact with anticoagulants

Diuretics

water pills eliminate excess fluid from body reduces amount of work heart has to do limit fluid buildup in the lungs improve exchange of gases in lungs

Oxygen

oxygen therapy especially for those who live in high altitude or have sleep apnea continuous use of oxygen through nasal prongs/oxygen mask relieve shortness of breath

Cardiotonics

strengthen the contractions of the heart heart does not need to beat as often to circulate adequate blood for body

Transplants

surgical interventions – considered only in extreme cases treatment for severe secondary PH if treatment of the underlying disorder fails surgically replace damage organs with healthy donated organs lung and/or heart transplantation most common : single-lung transplant, fewer complications than double-lung or heart-lung transplant lung transplant - improvement in structure and functioning of right ventricle major risks : rejection of transplanted organ, serious infection take immunosuppressant drugs for life – help reduce chance of rejection survival rate is about 60% per year and 37% per 5 years

Nitric Oxide

Inhaled formActs as direct smooth

muscle relaxant via activation of the guanylate cyclase system

Short therapeutic half lifeAmeliorates hypoxemia

and lowers PVR by direct pulmonary vasodilatation

Anticoagulation

Rationale for use is based on the presence of traditional risk factors for VTE, such as heart failure and sedentary lifestyle, thrombophilic predisposition, thrombotic changes in the pulmonary microcirculation and in the elastic pulmonary arteries.

Dose adjusted according to INR 2 - 3

Supplemental Oxygen

Low mixed venous oxygen saturation caused by low cardiac output and low minimally altered ventilation/ perfusion matching.

Improves quality of life and ↓ mortality in patients with PH due to chronic respiratory insufficiency.

Surgical Interventions

Atrial SeptostomyAllow R L shunting to increase systemic output

that, in spite of fall in the systemic arterial oxygen saturation, will produce an increase in systemic oxygen transport.

Shunt at the atrial level would allow decompression of the RA and RV, alleviating s/s of right heart failure.

Considered after short term failure of maximal medical therapy.

Heart / Lung Transplantation

1 year survival of 70%5 year survival of 50%

International Society for Heart and Lung Transplantation

Registry

Effective therapy for patients with end stage pulmonary vascular disease.

WHO Classification of Functional Status of Patients with PH

ClassClass DescriptionDescription

II Patients with PH in whom there is no limitation of usual physical Patients with PH in whom there is no limitation of usual physical activity; ordinary physical activity does not cause increased activity; ordinary physical activity does not cause increased dyspnea, fatigue, chest pain, or presyncope.dyspnea, fatigue, chest pain, or presyncope.

IIII Patients with PH who have mild limitation of physical activity. Patients with PH who have mild limitation of physical activity. There is no discomfort at rest, but normal physical activity causes There is no discomfort at rest, but normal physical activity causes increased dyspnea, fatigue, chest pain, or presyncope.increased dyspnea, fatigue, chest pain, or presyncope.

IIIIII Patients with PH who have a marked limitation of physical activity. Patients with PH who have a marked limitation of physical activity. There is no discomfort at rest, but less than ordinary activity There is no discomfort at rest, but less than ordinary activity causes increased dyspnea, fatigue, chest pain, or presyncope.causes increased dyspnea, fatigue, chest pain, or presyncope.

IVIV Patients with PH who are unable to perform any physical activity Patients with PH who are unable to perform any physical activity at rest and who may have signs of right ventricular failure. at rest and who may have signs of right ventricular failure. Dyspnea and/or fatigues may be present at rest, and symptoms Dyspnea and/or fatigues may be present at rest, and symptoms are increased by almost any physical activity.are increased by almost any physical activity.

Chest 2004:126 (Suppl), JACC 2004:43 (Suppl)

Thank You

Until recently, nothing much could be done for people with pulmonary hypertension. Before 1990, there were very few treatments available for PH and the survival rate was approximately two to four years. Since then, a number of exciting new treatments that are able to slow progression of the disease and may even reverse some of the damage to lungs and heart are gradually becoming available.

Some people do well on drugs; others may need a transplant. Some patients might also require supplemental oxygen delivered through nasal prongs or a mask if breathing becomes difficult whereas some need oxygen around the clock. In severely affected cases, a heart-lung, single lung of double lung transplantation may be appropriate.

PH patients respond differently to different medicines that are prescribed to dilate or relax blood vessels and no one drug can be said to be consistently effective in all patients. Because individual reactions vary, different drug have to be tried before chronic or long-term treatment begins.

During the course of disease, the amount and type of medicine may also have to be changed. To find out which medicine works best for a particular patient, the drugs should be evaluated via cardiac catheterization. This way, they can see the effect of the medicine on the patient’s heart and lungs. They can also adjust the dose to reduce the side effects such as systemic low BP, nausea, angina, headache etc that may occur.

To determine whether a drug is improving a patient’s condition, both the pulmonary pressure and the amount of blood being pumped by the heart (cardiac output) must be evaluated.

Calcium Channel Blockers

blocks entry of calcium into muscle cells of heart & arteries

improve ability of heart to pump blood

relaxes smooth muscle in walls of heart and blood vessels

amlodipine (Norvasc), diltiazem (Cardizem, Tiazac),

nifedipine (Adalat, Procardia), nicardipine (Cardene) etc.

only small number of people with PH respond to them

side effects – constipation, nausea, headache, rash, edema,

drowsiness, dizziness, low blood pressure

Blood Vessel Dilators

Prostacyclin

substance that acts like a hormone (prostaglandin) imitates behaviour of natural prostacyclin powerful vasodilator and anti-clotting agent prevent blood clots from forming given intravenously through catheter bridge to help those waiting for transplant Epoprostenol (Flolan) - 1st vasodilator approved by FDA Ilopost - inhaled through nebulizer Treprostinil - injected under skin side effects - jaw pain, nausea, leg cramps etc need comprehensive follow-up care

Endothelin Receptor Antagonists

available in pill form reverse effect of endothelin (blood vessels constriction) Bosentan (Tracleer) - may improve stamina of people with PH not for pregnant women need monthly liver monitoring - risk of liver complications

Phosphodiesterase Inhibitors

Revatio – contains sildenafil same active ingredient used in Viagra blocks the enzyme phosphodiesterase accentuates actions of nitric oxide opens blood vessels in the lungs - dilation side effect - vision problems

Lung and heart for transplant

Other treatment procedures

Dilation Atrial Septostomy

experimental procedure use in patient with severe PH makes a small hole in the heart, slowly enlarging it to relieve some of the pressure in the heart’s right side shunts blood across the atrial septum and into the left side of the heart similar to balloon atrial septostomy – naturally occurring hole present at birth is enlarged to help those with congenital heart defects

Other areas of research for treatment of PH includes gene therapy and stem cell research.

Pregnancy and PH

The consensus of medical opinion is that PH and pregnancy is very dangerous. The life of the mother and baby are put at great risk. Pregnancy can really take its toll on a woman’s body. For example, heart rate speeds up and the immune system does not work quite as well. For a woman whose body already has to deal with a severe illness, pregnancy can actually have catastrophic consequences. The risk of pregnancy-related death in women with PH is substantial – reported to be as high as 30-50%.

Some drugs commonly used to treat PH can be harmful to the developing fetus (e.g. warfarin). Because of this twofold risk to both mother and baby, use of some form of birth control to avoid pregnancy is strongly advised in women of childbearing age with PH.

Children and PH

Untreated PH in children worsens more quickly than the same condition in adults. Children also change more quickly than adults and have to be watched closely. However, with treatment, children appear to have an overall better prognosis than adults.

Children are responsive to the same treatments as adults. Treatment for PH is lifelong. The treatment used has to be individualized and adjusted according to how the child is responding.

Unfortunately, there is no minimum age for PH sufferers. Newborn, young children, teenagers and even in early adulthood, PH may occur.

A child with PH can still go to school, dance, play sports or ride a bike. Just like other children, a child with PH can help themselves by eating a healthy and balanced diet and have good rest periods.

It is really important to have a greater degree of caution in allowing other non-PH doctors prescribe medication for a child with PH.

Children and PH

It is hard but children with PH should be treated as normally as possible. The child will be happier and feel safer if they are treated just like the rest of the family.

News From Home

KUALA LUMPUR : Siti Salmah Jasni is on a heart-and-lung support machine and still in critical condition.

A statement issued by the National Heart Institute (IJN) said Siti Salmah is awake and able to respond to doctors.

Siti Salmah underwent a six-hour heart and lung transplant at 12.10am on Friday at IJN. She was suffering from pulmonary hypertension. The 18-year-old is the first in IJN's history to receive a combined heart and lung transplant.

The organs were harvested by a 10-member IJN team on Thursday night at the Sultanah Bahiyah Hospital in Kedah from a woman donor who became brain dead after a road accident

IJN thanked the donor's family for their generosity during their hour of grief. New Straits Times

2007/11/04

Recent advances in genetics and newer understandings in cell biology are providing fresh insights into the nature of this disease. New therapies offer an improved quality of life and increased survival rates in both adults and children.

References

http://www.medicinenet.com/script/main/art.asp?articlekey=77244http://www.medicinenet.com/pulmonary_hypertension/index.htmhttp://www.medicinenet.com/calcium_channel_blockers/article.htmwww.merck.com/mmhe/sec04/ch054/ch054a.htmlwww.mayoclinic.com/health/pulmonary-hypertension/DS00430www.nlm.nih.gov/medlineplus/pulmonaryhypertension.htmlwww.phassociation.orgwww.americanheart.org/presenter.jhtml?identifier=11076www.nhlbi.nih.gov/health/dci/Diseases/pah/pah_what.htmlhttp://www.pha-uk.com/living_with_ph/http://heart.health.ivillage.com/pulmonary/pulmonaryhypertension2.cfmwww.mater.ie/pha-ireland/html/what.htm.http://www.medicalook.com/Lung_diseases/Pulmonary_hypertension.htmlwww-ermm.cbcu.cam.ac.uk/04007513h.htm.home-2.tiscali.nl/~rsmid/index.html.http://www.nst.com.my/

THANK YOU FOR YOUR ATTENTION!!

AND HAVE A PLEASANT DAY!!