Pulmonary hypertension
Encyclopedia
In medicine
, pulmonary hypertension (PH) is an increase in blood pressure in the pulmonary artery
, pulmonary vein
, or pulmonary capillaries, together known as the lung
vasculature
, leading to shortness of breath, dizziness
, fainting, and other symptoms, all of which are exacerbated by exertion. Pulmonary hypertension can be a severe disease with a markedly decreased exercise tolerance and heart failure. It was first identified by Dr. Ernst von Romberg in 1891. According to the most recent classification, it can be one of five different types: arterial, venous, hypoxic, thromboembolic or miscellaneous.
, non-productive cough
, angina pectoris, fainting or syncope
, peripheral
edema (swelling around the ankles and feet), and rarely hemoptysis
(coughing up blood).
Pulmonary venous hypertension
typically presents with shortness of breath while lying flat or sleeping (orthopnea or paroxysmal nocturnal dyspnea), while pulmonary arterial hypertension (PAH) typically does not.
A detailed family history is established to determine whether the disease might be familial. A history of exposure to drugs such as cocaine
, methamphetamine
, alcohol
leading to cirrhosis
, and tobacco leading to emphysema
are considered significant. A physical examination
is performed to look for typical signs of pulmonary hypertension, including a loud S2 (pulmonic valve closure sound), (para)sternal heave, jugular venous distension, pedal edema
, ascites
, hepatojugular reflux
, clubbing etc. Evidence of tricuspid insufficiency
is also sought and, if present, is consistent with the presence of pulmonary hypertension.
A physical examination
is performed to look for typical signs of pulmonary hypertension. These include altered heart sounds
, such as a widely split S2 or second heart sound, a loud P2 or pulmonic valve
closure sound (part of the second heart sound), (para)sternal heave, possible S3 or third heart sound, and pulmonary regurgitation. Other signs include an elevated jugular venous pressure
, peripheral edema
(swelling of the ankles and feet), ascites
(abdominal swelling due to the accumulation of fluid), hepatojugular reflux
, and clubbing.
Further procedures are required to confirm the presence of pulmonary hypertension and exclude other possible diagnoses. These generally include pulmonary function tests; blood test
s to exclude HIV
, autoimmune diseases, and liver disease; electrocardiography (ECG); arterial blood gas
measurements; X-ray
s of the chest (followed by high-resolution CT scanning if interstitial lung disease is suspected); and ventilation-perfusion or V/Q scanning to exclude chronic thromboembolic pulmonary hypertension. Biopsy of the lung is usually not indicated unless the pulmonary hypertension is thought to be due to an underlying interstitial lung disease. But lung biopsies are fraught with risks of bleeding due to the high intrapulmonary blood pressure. Clinical improvement is often measured by a "six-minute walk test", i.e. the distance a patient can walk in six minutes. Stability and improvement in this measurement correlate with better survival. Blood BNP
level is also being used now to follow progress of patients with pulmonary hypertension.
Diagnosis of PAH requires the presence of pulmonary hypertension with two other conditions. Pulmonary artery occlusion pressure (PAOP or PCWP) must be less than 15 mm Hg (2000 Pa) and pulmonary vascular resistance (PVR) must be greater than 3 Wood units (240 dyn•s•cm−5 or 2.4 mN•s•cm−5).
Although pulmonary arterial pressure can be estimated on the basis of echocardiography
, pressure measurements with a Swan-Ganz catheter provides the most definite assessment. PAOP and PVR cannot be measured directly with echocardiography
. Therefore diagnosis of PAH requires right-sided cardiac catheterization
. A Swan-Ganz catheter can also measure the cardiac output
, which is far more important in measuring disease severity than the pulmonary arterial pressure.
Normal pulmonary arterial pressure in a person living at sea level has a mean value of 12–16 mm Hg (1600–2100 Pa). Pulmonary hypertension is present when mean pulmonary artery pressure exceeds 25 mm Hg (3300 Pa) at rest or 30 mm Hg (4000 Pa) with exercise.
Mean pulmonary artery pressure (mPAP) should not be confused with systolic pulmonary artery pressure (sPAP), which is often reported on echocardiogram reports. A systolic pressure of 40 mm Hg typically implies a mean pressure of more than 25 mm Hg. Roughly, mPAP = 0.61•sPAP + 2.
was the first to attempt classification of pulmonary hypertension. A distinction was made between primary and secondary PH, and primary PH was divided in the "arterial plexiform", "veno-occlusive" and "thromboembolic" forms. A second conference in 1998 at Évian-les-Bains
also addressed the causes of secondary PH (i.e. those due to other medical conditions), and in 2003, the 3rd World Symposium on Pulmonary Arterial Hypertension was convened in Venice to modify the classification based on new understandings of disease mechanisms. The revised system developed by this group provides the current framework for understanding pulmonary hypertension. The system includes several improvements over the former 1998 Evian Classification system. Risk factor descriptions were updated, and the classification of congenital systemic-to pulmonary shunts was revised. A new classification of genetic factors in PH was recommended, but not implemented because available data were judged to be inadequate.
The Venice 2003 Revised Classification system can be summarized as follows:
The classification does not include sickle cell disease,
Human herpesvirus 8, also associated with Kaposi's sarcoma
, has been demonstrated in patients with PAH, suggesting that this virus may play a role in its development. Recent studies have been unable to find an association between human herpesvirus 8 and idiopathic pulmonary arterial hypertension.
. This further increases the blood pressure within the lungs and impairs their blood flow. In addition, the increased workload of the heart causes hypertrophy
of the right ventricle
, making the heart less able to pump blood through the lungs, ultimately causing right heart failure (a condition known as cor pulmonale
). As the blood flowing through the lungs decreases, the left side of the heart receives less blood. This blood may also carry less oxygen than normal. Therefore it becomes harder and harder for the left side of the heart to pump to supply sufficient oxygen
to the rest of the body, especially during physical activity.
Pathogenesis in pulmonary venous hypertension (WHO Group II) is completely different. There is no obstruction to blood flow in the lungs. Instead, the left heart fails to pump blood efficiently, leading to pooling of blood in the lungs. This causes pulmonary edema
and pleural effusion
s.
In hypoxic pulmonary hypertension (WHO Group III), the low levels of oxygen are thought to cause vasoconstriction
or tightening of pulmonary arteries. This leads to a similar pathophysiology
as pulmonary arterial hypertension.
In chronic thromboembolic pulmonary hypertension (WHO Group IV), the blood vessels are blocked or narrowed with blood clots. Again, this leads to a similar pathophysiology
as pulmonary arterial hypertension.
Other forms of PAH are far more common. In scleroderma
the incidence has been estimated to be 6 to 60% of all patients, in rheumatoid arthritis
up to 21%, in systemic lupus erythematosus
4 to 14%, in portal hypertension
between 2 to 5%, in HIV about 0.5%, and in sickle cell disease ranging from 20 to 40%.
Diet pills such as Fen-Phen
produced an annual incidence of 25-50 per million per year.
Pulmonary venous hypertension is exceedingly common, since it occurs in most patients symptomatic with congestive heart failure.
Up to 4% of people who suffer a pulmonary embolism
go on to develop chronic thromboembolic disease including pulmonary hypertension.
Only about 1.1% of patients with COPD
develop pulmonary hypertension with no other disease to explain the high pressure. Sleep apnea
is usually associated with only very mild pulmonary hypertension, typically below the level of detection. On the other hand Pickwickian syndrome
(obesity-hypoventilation syndrome) is very commonly associated with right heart failure due to pulmonary hypertension.
, the treatment is to optimize left ventricular function by the use of diuretic
s, beta blocker
s, ACE inhibitor
s, etc., or to repair/replace the mitral valve
or aortic valve
.
In PAH, lifestyle changes, digoxin
, diuretic
s, oral anticoagulant
s, and oxygen therapy are considered conventional therapy, but have never been proven to be beneficial in a randomized, prospective manner.
High dose calcium channel blocker
s are useful in only 5% of IPAH patients who are vasoreactive by Swan-Ganz catheter. Unfortunately, calcium channel blockers have been largely misused, being prescribed to many patients with non-vasoreactive PAH, leading to excess morbidity and mortality. The criteria for vasoreactivity have changed. Only those patients whose mean pulmonary artery pressure falls by more than 10 mm Hg to less than 40 mm Hg with an unchanged or increased cardiac output when challenged with adenosine, epoprostenol, or nitric oxide
are considered vasoreactive. Of these, only half of the patients are responsive to calcium channel blocker
s in the long term.
A number of agents has recently been introduced for primary and secondary PAH. The trials supporting the use of these agents have been relatively small, and the only measure consistently used to compare their effectivity is the "6 minute walk test". Many have no data on mortality benefit or time to progression.
cells of the pulmonary arteries in patients with pulmonary arterial hypertension. Three of these pathways are important since they have been targeted with drugs — endothelin receptor antagonist
s, phosphodiesterase
type 5 inhibitors, and prostacyclin derivatives.
Because inexpensive generic drugs for this disease are not widely available, the World Health Organization does not include them in its model list of essential medicines
.
(prostaglandin
I2) is commonly considered the most effective treatment for PAH. Epoprostenol (synthetic prostacyclin
, marketed as Flolan) is given via continuous infusion that requires a semi-permanent central venous catheter
. This delivery system can cause sepsis
and thrombosis
. Flolan is unstable, and therefore has to be kept on ice during administration. Since it has a half-life of 3 to 5 minutes, the infusion has to be continuous (24/7), and interruption can be fatal. Other prostanoid
s have therefore been developed. Treprostinil
(Remodulin) can be given intravenously or subcutaneously, but the subcutaneous form can be very painful. An increased risk of sepsis with intravenous Remodulin has been reported by the CDC
. Iloprost
(Ilomedin) is also used in Europe intravenously and has a longer half life. Iloprost
(marketed as Ventavis) was the only inhaled form of prostacyclin approved for use in the US and Europe, until the inhaled form of treprostinil
was approved by the FDA in July 2009 and is marketed under the trade name Tyvaso. The inhaled form of administration has the advantage of selective deposition in the lungs with less systemic side effects, however coughing and throat irritation commonly occur. Oral and inhaled forms of Remodulin are under development. Beraprost
is an oral prostanoid available in South Korea and Japan.
receptor antagonist bosentan
(marketed as Tracleer) was approved in 2001. Sitaxentan, a selective endothelin receptor antagonist that blocks only the action of ETA, has been approved for use in Canada, Australia, and the European Union, to be marketed under the name Thelin. Sitaxentan has not been approved for marketing by the U.S. Food and Drug Administration
(FDA). In 2010, Thelin was withdrawn by Pfizer due to severe side effects. A new trial to address the FDA's concerns will begin in 2008. A similar drug, ambrisentan
is marketed as Letairis in U.S. by Gilead Sciences
. In addition, another dual/nonselective endothelin antagonist, Actelion-1, from the makers of Tracleer, will enter clinical trials in 2008.
, a selective inhibitor of cGMP specific phosphodiesterase type 5
(PDE5), for the treatment of PAH in 2005. It is marketed for PAH as Revatio. In 2009, they also approved Tadalafil
, another PDE5 inhibitor, marketed under the name Adcirca.
(sGC) is the intracellular receptor for NO
. , the sGC activators cinaciguat
and riociguat
are undergoing clinical trials for the treatment of PAH.
is a surgical procedure that creates a communication between the right and left atria. It relieves pressure on the right side of the heart, but at the cost of lower oxygen levels in blood (hypoxia).
Lung transplantation
cures pulmonary arterial hypertension, but leaves the patient with the complications of transplantation, and a post-surgical median
survival of just over five years.
Pulmonary thromboendarterectomy
(PTE) is a surgical procedure that is used for chronic thromboembolic pulmonary hypertension. It is the surgical removal of an organized thrombus
(clot) along with the lining of the pulmonary artery; it is a very difficult, major procedure that is currently performed in a few select centers. Case series show remarkable success in most patients.
Treatment regimens for hypoxic and miscellaneous varieties of pulmonary hypertension have not been established. However, studies of several agents are currently enrolling patients. Many physicians will treat these diseases with the same medications as for PAH, until better options become available. Such treatment is called off-label use
.
). Although this figure is widely quoted, it is probably irrelevant today. Outcomes have changed dramatically over the last two decades. This may be because of newer drug therapy, better overall care, and earlier diagnosis (lead time bias). A recent outcome study of those patients who had started treatment with bosentan (Tracleer) showed that 89% patients were alive at 2 years. With multiple agents now available, combination therapy is increasingly used. Impact of these agents on survival is not known, since many of them have been developed only recently. It would not be unreasonable to expect median survival to extend past 10 years in the near future.
Levels of mortality are very high in pregnant women with severe pulmonary hypertension. Pregnancy is sometimes described as contraindicated in these women.
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
, pulmonary hypertension (PH) is an increase in blood pressure in the pulmonary artery
Pulmonary artery
The pulmonary arteries carry deoxygenated blood from the heart to the lungs. They are the only arteries that carry deoxygenated blood....
, pulmonary vein
Pulmonary vein
The pulmonary veins are large blood vessels that carry blood from the lungs to the left atrium of the heart. In humans there are four pulmonary veins, two from each lung...
, or pulmonary capillaries, together known as the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
vasculature
Pulmonary circulation
Pulmonary circulation is the half portion of the cardiovascular system which carries Oxygen-depleted Blood away from the heart, to the Lungs, and returns oxygenated blood back to the heart. Encyclopedic description and discovery of the pulmonary circulation is widely attributed to Doctor Ibn...
, leading to shortness of breath, dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
, fainting, and other symptoms, all of which are exacerbated by exertion. Pulmonary hypertension can be a severe disease with a markedly decreased exercise tolerance and heart failure. It was first identified by Dr. Ernst von Romberg in 1891. According to the most recent classification, it can be one of five different types: arterial, venous, hypoxic, thromboembolic or miscellaneous.
Signs and symptoms
Because symptoms may develop very gradually, patients may delay seeing a physician for years. Common symptoms are shortness of breath, fatigueFatigue (physical)
Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...
, non-productive cough
Cough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
, angina pectoris, fainting or syncope
Syncope (medicine)
Syncope , the medical term for fainting, is precisely defined as a transient loss of consciousness and postural tone characterized by rapid onset, short duration, and spontaneous recovery due to global cerebral hypoperfusion that most often results from hypotension.Many forms of syncope are...
, peripheral
Peripheral
A peripheral is a device attached to a host computer, but not part of it, and is more or less dependent on the host. It expands the host's capabilities, but does not form part of the core computer architecture....
edema (swelling around the ankles and feet), and rarely hemoptysis
Hemoptysis
Hemoptysis or haemoptysis is the expectoration of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis is the expectoration (coughing up) of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis ...
(coughing up blood).
Pulmonary venous hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
typically presents with shortness of breath while lying flat or sleeping (orthopnea or paroxysmal nocturnal dyspnea), while pulmonary arterial hypertension (PAH) typically does not.
A detailed family history is established to determine whether the disease might be familial. A history of exposure to drugs such as cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
, methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
, alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
leading to cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
, and tobacco leading to emphysema
Emphysema
Emphysema is a long-term, progressive disease of the lungs that primarily causes shortness of breath. In people with emphysema, the tissues necessary to support the physical shape and function of the lungs are destroyed. It is included in a group of diseases called chronic obstructive pulmonary...
are considered significant. A physical examination
Physical examination
Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...
is performed to look for typical signs of pulmonary hypertension, including a loud S2 (pulmonic valve closure sound), (para)sternal heave, jugular venous distension, pedal edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
, ascites
Ascites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
, hepatojugular reflux
Abdominojugular test
The abdominojugular test , also known as hepatojugular reflex or reflux, is used as an alternate test for measuring jugular venous pressure through the distension or swelling of the internal jugular vein...
, clubbing etc. Evidence of tricuspid insufficiency
Tricuspid insufficiency
Tricuspid insufficiency , a valvular heart disease also called tricuspid regurgitation , refers to the failure of the heart's tricuspid valve to close properly during systole. As a result, with each heart beat some blood passes from the right ventricle to the right atrium, the opposite of the...
is also sought and, if present, is consistent with the presence of pulmonary hypertension.
Diagnosis
Because pulmonary hypertension can be of five major types, a series of tests must be performed to distinguish pulmonary arterial hypertension from venous, hypoxic, thromboembolic, or miscellaneous varieties.A physical examination
Physical examination
Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...
is performed to look for typical signs of pulmonary hypertension. These include altered heart sounds
Heart sounds
Heart sounds, or heartbeats, are the noises generated by the beating heart and the resultant flow of blood through it...
, such as a widely split S2 or second heart sound, a loud P2 or pulmonic valve
Pulmonary valve
The pulmonary valve is the semilunar valve of the heart that lies between the right ventricle and the pulmonary artery and has three cusps. Similar to the aortic valve, the pulmonary valve opens in ventricular systole, when the pressure in the right ventricle rises above the pressure in the...
closure sound (part of the second heart sound), (para)sternal heave, possible S3 or third heart sound, and pulmonary regurgitation. Other signs include an elevated jugular venous pressure
Jugular venous pressure
The jugular venous pressure is the indirectly observed pressure over the venous system...
, peripheral edema
Peripheral edema
Peripheral edema is the swelling of tissues, usually in the lower limbs, due to the accumulation of fluids.The condition is commonly associated with aging, but can be caused by many other conditions, including congestive heart failure, trauma, alcoholism, altitude sickness, pregnancy,...
(swelling of the ankles and feet), ascites
Ascites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
(abdominal swelling due to the accumulation of fluid), hepatojugular reflux
Abdominojugular test
The abdominojugular test , also known as hepatojugular reflex or reflux, is used as an alternate test for measuring jugular venous pressure through the distension or swelling of the internal jugular vein...
, and clubbing.
Further procedures are required to confirm the presence of pulmonary hypertension and exclude other possible diagnoses. These generally include pulmonary function tests; blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s to exclude HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, autoimmune diseases, and liver disease; electrocardiography (ECG); arterial blood gas
Arterial blood gas
An arterial blood gas is a blood test that is performed using blood from an artery. It involves puncturing an artery with a thin needle and syringe and drawing a small volume of blood. The most common puncture site is the radial artery at the wrist, but sometimes the femoral artery in the groin or...
measurements; X-ray
X-ray
X-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
s of the chest (followed by high-resolution CT scanning if interstitial lung disease is suspected); and ventilation-perfusion or V/Q scanning to exclude chronic thromboembolic pulmonary hypertension. Biopsy of the lung is usually not indicated unless the pulmonary hypertension is thought to be due to an underlying interstitial lung disease. But lung biopsies are fraught with risks of bleeding due to the high intrapulmonary blood pressure. Clinical improvement is often measured by a "six-minute walk test", i.e. the distance a patient can walk in six minutes. Stability and improvement in this measurement correlate with better survival. Blood BNP
Brain natriuretic peptide
Brain natriuretic peptide , now known as B-type natriuretic peptide or GC-B, is a 32 amino acid polypeptide secreted by the ventricles of the heart in response to excessive stretching of heart muscle cells...
level is also being used now to follow progress of patients with pulmonary hypertension.
Diagnosis of PAH requires the presence of pulmonary hypertension with two other conditions. Pulmonary artery occlusion pressure (PAOP or PCWP) must be less than 15 mm Hg (2000 Pa) and pulmonary vascular resistance (PVR) must be greater than 3 Wood units (240 dyn•s•cm−5 or 2.4 mN•s•cm−5).
Although pulmonary arterial pressure can be estimated on the basis of echocardiography
Echocardiography
An echocardiogram, often referred to in the medical community as a cardiac ECHO or simply an ECHO, is a sonogram of the heart . Also known as a cardiac ultrasound, it uses standard ultrasound techniques to image two-dimensional slices of the heart...
, pressure measurements with a Swan-Ganz catheter provides the most definite assessment. PAOP and PVR cannot be measured directly with echocardiography
Echocardiography
An echocardiogram, often referred to in the medical community as a cardiac ECHO or simply an ECHO, is a sonogram of the heart . Also known as a cardiac ultrasound, it uses standard ultrasound techniques to image two-dimensional slices of the heart...
. Therefore diagnosis of PAH requires right-sided cardiac catheterization
Cardiac catheterization
Cardiac catheterization is the insertion of a catheter into a chamber or vessel of the heart. This is done for both investigational and interventional purposes...
. A Swan-Ganz catheter can also measure the cardiac output
Cardiac output
Cardiac output is the volume of blood being pumped by the heart, in particular by a left or right ventricle in the time interval of one minute. CO may be measured in many ways, for example dm3/min...
, which is far more important in measuring disease severity than the pulmonary arterial pressure.
Normal pulmonary arterial pressure in a person living at sea level has a mean value of 12–16 mm Hg (1600–2100 Pa). Pulmonary hypertension is present when mean pulmonary artery pressure exceeds 25 mm Hg (3300 Pa) at rest or 30 mm Hg (4000 Pa) with exercise.
Mean pulmonary artery pressure (mPAP) should not be confused with systolic pulmonary artery pressure (sPAP), which is often reported on echocardiogram reports. A systolic pressure of 40 mm Hg typically implies a mean pressure of more than 25 mm Hg. Roughly, mPAP = 0.61•sPAP + 2.
Causes and classification
A 1973 meeting organized by the World Health OrganizationWorld Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
was the first to attempt classification of pulmonary hypertension. A distinction was made between primary and secondary PH, and primary PH was divided in the "arterial plexiform", "veno-occlusive" and "thromboembolic" forms. A second conference in 1998 at Évian-les-Bains
Évian-les-Bains
Évian-les-Bains or Évian is a commune in the northern part of the Haute-Savoie department in the Rhône-Alpes region in south-eastern France...
also addressed the causes of secondary PH (i.e. those due to other medical conditions), and in 2003, the 3rd World Symposium on Pulmonary Arterial Hypertension was convened in Venice to modify the classification based on new understandings of disease mechanisms. The revised system developed by this group provides the current framework for understanding pulmonary hypertension. The system includes several improvements over the former 1998 Evian Classification system. Risk factor descriptions were updated, and the classification of congenital systemic-to pulmonary shunts was revised. A new classification of genetic factors in PH was recommended, but not implemented because available data were judged to be inadequate.
The Venice 2003 Revised Classification system can be summarized as follows:
- WHO Group I - Pulmonary arterial hypertension (PAH)
- Idiopathic (IPAH)
- Familial (FPAH)
- Associated with other diseases (APAH): collagen vascular disease (e.g. sclerodermaSclerodermaSystemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...
), congenital shunts between the systemic and pulmonary circulation, portal hypertensionPortal hypertensionIn medicine, portal hypertension is hypertension in the portal vein and its tributaries.It is often defined as a portal pressure gradient of 10 mmHg or greater.-Causes:Causes can be divided into prehepatic, intrahepatic, and posthepatic...
, HIVHIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
infection, drugs, toxins, or other diseases or disorders - Associated with venous or capillary disease
- WHO Group II - Pulmonary hypertension associated with left heart disease
- Atrial or ventricular disease
- Valvular disease (e.g. mitral stenosisMitral stenosisMitral stenosis is a valvular heart disease characterized by the narrowing of the orifice of the mitral valve of the heart.-Signs and symptoms:Symptoms of mitral stenosis include:...
)
- WHO Group III - Pulmonary hypertension associated with lung diseases and/or hypoxemia
- Chronic obstructive pulmonary diseaseChronic obstructive pulmonary diseaseChronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...
(COPD), interstitial lung disease (ILD) - Sleep-disordered breathing, alveolar hypoventilation
- Chronic exposure to high altitude
- Developmental lung abnormalities
- Chronic obstructive pulmonary disease
- WHO Group IV - Pulmonary hypertension due to chronic thrombotic and/or embolic disease
- Pulmonary embolismPulmonary embolismPulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
in the proximal or distal pulmonary arteries - Embolization of other matter, such as tumorTumorA tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
cells or parasites
- Pulmonary embolism
- WHO Group V - Miscellaneous
The classification does not include sickle cell disease,
Human herpesvirus 8, also associated with Kaposi's sarcoma
Kaposi's sarcoma
Kaposi's sarcoma is a tumor caused by Human herpesvirus 8 , also known as Kaposi's sarcoma-associated herpesvirus . It was originally described by Moritz Kaposi , a Hungarian dermatologist practicing at the University of Vienna in 1872. It became more widely known as one of the AIDS defining...
, has been demonstrated in patients with PAH, suggesting that this virus may play a role in its development. Recent studies have been unable to find an association between human herpesvirus 8 and idiopathic pulmonary arterial hypertension.
Pathogenesis
Whatever the initial cause, pulmonary arterial hypertension (WHO Group I) involves the vasoconstriction or tightening of blood vessels connected to and within the lungs. This makes it harder for the heart to pump blood through the lungs, much as it is harder to make water flow through a narrow pipe as opposed to a wide one. Over time, the affected blood vessels become both stiffer and thicker, in a process known as fibrosisFibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
. This further increases the blood pressure within the lungs and impairs their blood flow. In addition, the increased workload of the heart causes hypertrophy
Ventricular hypertrophy
Ventricular hypertrophy is the enlargement of ventricles in the heart. Although left ventricular hypertrophy is more common, enlargement can also occur in the right ventricle, or both ventricles.- Physiology :...
of the right ventricle
Right ventricle
The right ventricle is one of four chambers in the human heart. It receives deoxygenated blood from the right atrium via the tricuspid valve, and pumps it into the pulmonary artery via the pulmonary valve and pulmonary trunk....
, making the heart less able to pump blood through the lungs, ultimately causing right heart failure (a condition known as cor pulmonale
Cor pulmonale
Cor pulmonale or pulmonary heart disease is enlargement of the right ventricle of the heart as a response to increased resistance or high blood pressure in the lungs ....
). As the blood flowing through the lungs decreases, the left side of the heart receives less blood. This blood may also carry less oxygen than normal. Therefore it becomes harder and harder for the left side of the heart to pump to supply sufficient oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
to the rest of the body, especially during physical activity.
Pathogenesis in pulmonary venous hypertension (WHO Group II) is completely different. There is no obstruction to blood flow in the lungs. Instead, the left heart fails to pump blood efficiently, leading to pooling of blood in the lungs. This causes pulmonary edema
Pulmonary edema
Pulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure...
and pleural effusion
Pleural effusion
Pleural effusion is excess fluid that accumulates between the two pleural layers, the fluid-filled space that surrounds the lungs. Excessive amounts of such fluid can impair breathing by limiting the expansion of the lungs during ventilation.-Pathophysiology:...
s.
In hypoxic pulmonary hypertension (WHO Group III), the low levels of oxygen are thought to cause vasoconstriction
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...
or tightening of pulmonary arteries. This leads to a similar pathophysiology
Pathophysiology
Pathophysiology is the study of the changes of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from an abnormal syndrome...
as pulmonary arterial hypertension.
In chronic thromboembolic pulmonary hypertension (WHO Group IV), the blood vessels are blocked or narrowed with blood clots. Again, this leads to a similar pathophysiology
Pathophysiology
Pathophysiology is the study of the changes of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from an abnormal syndrome...
as pulmonary arterial hypertension.
Epidemiology
IPAH is a rare disease with an incidence of about 2-3 per million per year and a prevalence of about 15 per million. Adult females are almost three times as likely to present with IPAH than adult males. The presentation of IPAH within children is more evenly split along gender lines.Other forms of PAH are far more common. In scleroderma
Scleroderma
Systemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...
the incidence has been estimated to be 6 to 60% of all patients, in rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
up to 21%, in systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
4 to 14%, in portal hypertension
Portal hypertension
In medicine, portal hypertension is hypertension in the portal vein and its tributaries.It is often defined as a portal pressure gradient of 10 mmHg or greater.-Causes:Causes can be divided into prehepatic, intrahepatic, and posthepatic...
between 2 to 5%, in HIV about 0.5%, and in sickle cell disease ranging from 20 to 40%.
Diet pills such as Fen-Phen
Fen-phen
The drug combination fenfluramine/phentermine, usually called fen-phen, is an anti-obesity treatment that utilizes two anorectics. Fenfluramine, its S-enantiomer dexfenfluramine, and a few other serotonin agonists were shown to cause potentially fatal pulmonary hypertension and heart valve...
produced an annual incidence of 25-50 per million per year.
Pulmonary venous hypertension is exceedingly common, since it occurs in most patients symptomatic with congestive heart failure.
Up to 4% of people who suffer a pulmonary embolism
Pulmonary embolism
Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
go on to develop chronic thromboembolic disease including pulmonary hypertension.
Only about 1.1% of patients with COPD
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...
develop pulmonary hypertension with no other disease to explain the high pressure. Sleep apnea
Sleep apnea
Sleep apnea is a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may occur 5 to 30 times or more an hour. Similarly, each abnormally low...
is usually associated with only very mild pulmonary hypertension, typically below the level of detection. On the other hand Pickwickian syndrome
Pickwickian syndrome
Obesity hypoventilation syndrome is a condition in which severely overweight people fail to breathe rapidly enough or deeply enough, resulting in low blood oxygen levels and high blood carbon dioxide levels...
(obesity-hypoventilation syndrome) is very commonly associated with right heart failure due to pulmonary hypertension.
Treatment
Treatment is determined by whether the PH is arterial, venous, hypoxic, thromboembolic, or miscellaneous. Since pulmonary venous hypertension is synonymous with congestive heart failureCongestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
, the treatment is to optimize left ventricular function by the use of diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
s, beta blocker
Beta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...
s, ACE inhibitor
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
s, etc., or to repair/replace the mitral valve
Mitral valve
The mitral valve is a dual-flap valve in the heart that lies between the left atrium and the left ventricle...
or aortic valve
Aortic valve
The aortic valve is one of the valves of the heart. It is normally tricuspid , although in 1% of the population it is found to be congenitally bicuspid . It lies between the left ventricle and the aorta....
.
In PAH, lifestyle changes, digoxin
Digoxin
Digoxin INN , also known as digitalis, is a purified cardiac glycoside and extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin...
, diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
s, oral anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
s, and oxygen therapy are considered conventional therapy, but have never been proven to be beneficial in a randomized, prospective manner.
High dose calcium channel blocker
Calcium channel blocker
A calcium channel blocker is a chemical that disrupts the movement of calcium through calcium channels.CCB drugs devised to target neurons are used as antiepileptics. However, the most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with...
s are useful in only 5% of IPAH patients who are vasoreactive by Swan-Ganz catheter. Unfortunately, calcium channel blockers have been largely misused, being prescribed to many patients with non-vasoreactive PAH, leading to excess morbidity and mortality. The criteria for vasoreactivity have changed. Only those patients whose mean pulmonary artery pressure falls by more than 10 mm Hg to less than 40 mm Hg with an unchanged or increased cardiac output when challenged with adenosine, epoprostenol, or nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
are considered vasoreactive. Of these, only half of the patients are responsive to calcium channel blocker
Calcium channel blocker
A calcium channel blocker is a chemical that disrupts the movement of calcium through calcium channels.CCB drugs devised to target neurons are used as antiepileptics. However, the most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with...
s in the long term.
A number of agents has recently been introduced for primary and secondary PAH. The trials supporting the use of these agents have been relatively small, and the only measure consistently used to compare their effectivity is the "6 minute walk test". Many have no data on mortality benefit or time to progression.
Vasoactive substances
Many pathways are involved in the abnormal proliferation and contraction of the smooth muscleSmooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
cells of the pulmonary arteries in patients with pulmonary arterial hypertension. Three of these pathways are important since they have been targeted with drugs — endothelin receptor antagonist
Endothelin receptor antagonist
A endothelin receptor antagonist is a drug that blocks endothelin receptors.Three main kinds of ERAs exist:* selective ETA receptor antagonists , which affect endothelin A receptors....
s, phosphodiesterase
Phosphodiesterase
A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...
type 5 inhibitors, and prostacyclin derivatives.
Because inexpensive generic drugs for this disease are not widely available, the World Health Organization does not include them in its model list of essential medicines
Essential medicines
Essential medicines, as defined by the World Health Organization are "those drugs that satisfy the health care needs of the majority of the population; they should therefore be available at all times in adequate amounts and in appropriate dosage forms, at a price the community can afford."The WHO...
.
Prostaglandins
ProstacyclinProstacyclin
Prostacyclin is a member of the family of lipid molecules known as eicosanoids.As a drug, it is also known as "epoprostenol". The terms are sometimes used interchangeably.-History:...
(prostaglandin
Prostaglandin
A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....
I2) is commonly considered the most effective treatment for PAH. Epoprostenol (synthetic prostacyclin
Prostacyclin
Prostacyclin is a member of the family of lipid molecules known as eicosanoids.As a drug, it is also known as "epoprostenol". The terms are sometimes used interchangeably.-History:...
, marketed as Flolan) is given via continuous infusion that requires a semi-permanent central venous catheter
Central venous catheter
In medicine, a central venous catheter is a catheter placed into a large vein in the neck , chest or groin...
. This delivery system can cause sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
and thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
. Flolan is unstable, and therefore has to be kept on ice during administration. Since it has a half-life of 3 to 5 minutes, the infusion has to be continuous (24/7), and interruption can be fatal. Other prostanoid
Prostanoid
Prostanoid is the term used to describe a subclass of eicosanoids consisting of: the prostaglandins , the thromboxanes and the prostacyclins - Biosynthesis : Cyclooxygenase catalyzes the conversion of the free essential fatty acids to...
s have therefore been developed. Treprostinil
Treprostinil
Treprostinil is a synthetic analog of prostacyclin .-History:...
(Remodulin) can be given intravenously or subcutaneously, but the subcutaneous form can be very painful. An increased risk of sepsis with intravenous Remodulin has been reported by the CDC
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
. Iloprost
Iloprost
Iloprost is a drug used to treat pulmonary arterial hypertension , scleroderma, Raynaud's phenomenon and ischemia. It was developed by the pharmaceutical company Schering AG and is marketed by Bayer Schering Pharma AG in Europe and Actelion Pharmaceuticals in the USA.-Clinical pharmacology:Iloprost...
(Ilomedin) is also used in Europe intravenously and has a longer half life. Iloprost
Iloprost
Iloprost is a drug used to treat pulmonary arterial hypertension , scleroderma, Raynaud's phenomenon and ischemia. It was developed by the pharmaceutical company Schering AG and is marketed by Bayer Schering Pharma AG in Europe and Actelion Pharmaceuticals in the USA.-Clinical pharmacology:Iloprost...
(marketed as Ventavis) was the only inhaled form of prostacyclin approved for use in the US and Europe, until the inhaled form of treprostinil
Treprostinil
Treprostinil is a synthetic analog of prostacyclin .-History:...
was approved by the FDA in July 2009 and is marketed under the trade name Tyvaso. The inhaled form of administration has the advantage of selective deposition in the lungs with less systemic side effects, however coughing and throat irritation commonly occur. Oral and inhaled forms of Remodulin are under development. Beraprost
Beraprost
Beraprost is a synthetic analogue of prostacyclin, under clinical trials for the treatment of pulmonary hypertension. It is also being studied for use in avoiding reperfusion injury.-Clinical pharmacology:...
is an oral prostanoid available in South Korea and Japan.
Endothelin receptor antagonists
The dual (ETA and ETB) endothelinEndothelin
Endothelins are proteins that constrict blood vessels and raise blood pressure. They are normally kept in balance by other mechanisms, but when they are over-expressed, they contribute to high blood pressure and heart disease....
receptor antagonist bosentan
Bosentan
Bosentan is a dual endothelin receptor antagonist used in the treatment of pulmonary artery hypertension . It is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Tracleer.-Mechanism of action:Bosentan is...
(marketed as Tracleer) was approved in 2001. Sitaxentan, a selective endothelin receptor antagonist that blocks only the action of ETA, has been approved for use in Canada, Australia, and the European Union, to be marketed under the name Thelin. Sitaxentan has not been approved for marketing by the U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA). In 2010, Thelin was withdrawn by Pfizer due to severe side effects. A new trial to address the FDA's concerns will begin in 2008. A similar drug, ambrisentan
Ambrisentan
Ambrisentan is a drug indicated for use in the treatment of pulmonary hypertension.It functions as an endothelin receptor antagonist, and is selective for the type A endothelin receptor ....
is marketed as Letairis in U.S. by Gilead Sciences
Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes therapeutics. For many years since the company was founded, the company concentrated primarily on antiviral drugs to treat patients infected with HIV, hepatitis B or influenza. In 2006, Gilead acquired two...
. In addition, another dual/nonselective endothelin antagonist, Actelion-1, from the makers of Tracleer, will enter clinical trials in 2008.
Phosphodiesterase type 5 inhibitors
The U.S. FDA approved SildenafilSildenafil
Sildenafil citrate, sold as Viagra, Revatio and under various other trade names, is a drug used to treat erectile dysfunction and pulmonary arterial hypertension . It was originally developed by British scientists and then brought to market by the US-based pharmaceutical company Pfizer...
, a selective inhibitor of cGMP specific phosphodiesterase type 5
CGMP specific phosphodiesterase type 5
cGMP-specific phosphodiesterase type 5 is an enzyme from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina....
(PDE5), for the treatment of PAH in 2005. It is marketed for PAH as Revatio. In 2009, they also approved Tadalafil
Tadalafil
Tadalafil is a PDE5 inhibitor, currently marketed in pill form for treating erectile dysfunction under the name Cialis; and under the name Adcirca for the treatment of pulmonary arterial hypertension...
, another PDE5 inhibitor, marketed under the name Adcirca.
Activators of soluble guanylate cyclase
Soluble guanylate cyclaseGuanylate cyclase
-Reaction:Guanylate cyclase catalyzes the reaction of guanosine triphosphate to 3',5'-cyclic guanosine monophosphate and pyrophosphate:-Types:...
(sGC) is the intracellular receptor for NO
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
. , the sGC activators cinaciguat
Cinaciguat
Cinaciguat is an experimental drug for the treatment of acute decompensated heart failure.-Mechanism of action:Cinaciguat activates the soluble guanylate cyclase which is a receptor for nitric oxide...
and riociguat
Riociguat
Riociguat is a novel drug that is currently in clinical development by Bayer. It is a stimulator of soluble guanylate cyclase...
are undergoing clinical trials for the treatment of PAH.
Surgical
Atrial septostomyAtrial septostomy
Atrial septostomy is a surgical procedure in which a small hole is created between the upper two chambers of the heart, the atria. This procedure is primarily used to treat dextro-Transposition of the great arteries or d-TGA , a life-threatening cyanotic congenital heart defect seen in infants...
is a surgical procedure that creates a communication between the right and left atria. It relieves pressure on the right side of the heart, but at the cost of lower oxygen levels in blood (hypoxia).
Lung transplantation
Lung transplantation
Lung transplantation, or pulmonary transplantation is a surgical procedure in which a patient's diseased lungs are partially or totally replaced by lungs which come from a donor...
cures pulmonary arterial hypertension, but leaves the patient with the complications of transplantation, and a post-surgical median
Median
In probability theory and statistics, a median is described as the numerical value separating the higher half of a sample, a population, or a probability distribution, from the lower half. The median of a finite list of numbers can be found by arranging all the observations from lowest value to...
survival of just over five years.
Pulmonary thromboendarterectomy
Pulmonary thromboendarterectomy
In thoracic surgery, a pulmonary thromboendarterectomy, PTE, is an operation that removes organized clotted blood from the pulmonary arteries.-Indication:...
(PTE) is a surgical procedure that is used for chronic thromboembolic pulmonary hypertension. It is the surgical removal of an organized thrombus
Thrombus
A thrombus , or blood clot, is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system...
(clot) along with the lining of the pulmonary artery; it is a very difficult, major procedure that is currently performed in a few select centers. Case series show remarkable success in most patients.
Treatment regimens for hypoxic and miscellaneous varieties of pulmonary hypertension have not been established. However, studies of several agents are currently enrolling patients. Many physicians will treat these diseases with the same medications as for PAH, until better options become available. Such treatment is called off-label use
Off-label use
Off-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration...
.
Monitoring
Patients are normally monitored through commonly available tests such as:- pulse oximetryPulse oximetryPulse oximetry is a non-invasive method allowing the monitoring of the oxygenation of a patient's hemoglobin.A sensor is placed on a thin part of the patient's body, usually a fingertip or earlobe, or in the case of an infant, across a foot....
- arterial blood gasArterial blood gasAn arterial blood gas is a blood test that is performed using blood from an artery. It involves puncturing an artery with a thin needle and syringe and drawing a small volume of blood. The most common puncture site is the radial artery at the wrist, but sometimes the femoral artery in the groin or...
tests - chest X-rayChest X-rayIn medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...
s - serial ECG tests
- serial echocardiographyEchocardiographyAn echocardiogram, often referred to in the medical community as a cardiac ECHO or simply an ECHO, is a sonogram of the heart . Also known as a cardiac ultrasound, it uses standard ultrasound techniques to image two-dimensional slices of the heart...
- spirometrySpirometrySpirometry is the most common of the pulmonary function tests , measuring lung function, specifically the measurement of the amount and/or speed of air that can be inhaled and exhaled...
or more advanced lung function studies
Prognosis
The NIH IPAH registry from the 1980s showed an untreated median survival of 2–3 years from time of diagnosis, with the cause of death usually being right ventricular failure (cor pulmonaleCor pulmonale
Cor pulmonale or pulmonary heart disease is enlargement of the right ventricle of the heart as a response to increased resistance or high blood pressure in the lungs ....
). Although this figure is widely quoted, it is probably irrelevant today. Outcomes have changed dramatically over the last two decades. This may be because of newer drug therapy, better overall care, and earlier diagnosis (lead time bias). A recent outcome study of those patients who had started treatment with bosentan (Tracleer) showed that 89% patients were alive at 2 years. With multiple agents now available, combination therapy is increasingly used. Impact of these agents on survival is not known, since many of them have been developed only recently. It would not be unreasonable to expect median survival to extend past 10 years in the near future.
Levels of mortality are very high in pregnant women with severe pulmonary hypertension. Pregnancy is sometimes described as contraindicated in these women.
External links
- The Merck Manual Home Edition: Pulmonary Hypertension
- Pulmonary Hypertension Association
- PH Central - the internet resource for Pulmonary Arterial Hypertension
- Facts About Primary Pulmonary Hypertension from the National Heart, Lung, and Blood InstituteNational Heart, Lung, and Blood InstituteThe National Heart, Lung, and Blood Institute is a division of the National Institutes of Health, located in Bethesda, Maryland...
(NHLBI) - Webcast: The Changing World of Pulmonary Arterial Hypertension Therapies - American College of CHEST Physicians
- GeneReviews/NCBI/NIH/UW entry on Heritable Pulmonary Arterial Hypertension
- OMIM entries on Heritable Pulmonary Arterial Hypertension