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. Depending on the cause, pulmonary hypertension can be a severe disease with a markedly decreased exercise tolerance and right-sided heart failure. It was first identified by Dr Ernst von Romberg in 1891.^[1] It can be one of five different types, arterial, venous, hypoxic, thromboembolic, or miscellaneous. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ... // I00-I99 - Diseases of the circulatory system (I00-I02) Acute rheumatic fever (I00) Rheumatic fever without mention of heart involvement (I01) Rheumatic fever with heart involvement (I02) Rheumatic chorea (I05-I09) Chronic rheumatic heart diseases (I05) Rheumatic mitral valve diseases (I050) Mitral stenosis (I051) Rheumatic mitral insufficiency (I06) Rheumatic aortic... // I00-I99 - Diseases of the circulatory system (I00-I02) Acute rheumatic fever (I00) Rheumatic fever without mention of heart involvement (I01) Rheumatic fever with heart involvement (I02) Rheumatic chorea (I05-I09) Chronic rheumatic heart diseases (I05) Rheumatic mitral valve diseases (I050) Mitral stenosis (I051) Rheumatic mitral insufficiency (I06) Rheumatic aortic... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... For the chemical substances known as medicines, see medication. ... The pulmonary arteries carry blood from the heart to the lungs. ... The pulmonary veins carry oxygen-rich blood from the lungs to the left atrium of the heart. ... Human respiratory system The lungs flank the heart and great vessels in the chest cavity. ... Pulmonary circulation is the 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. ... Dyspnea (R06. ... // Pre-syncope is a sensation of feeling faint. ... It has been suggested that Central Ischaemic Response be merged into this article or section. ...

Although primary pulmonary hypertension is ideopathic (meaning of unknown cause) and secondary pulmonary hypertension (meaning due to another medical condition) still persist in materials disseminated to patients and the general public, these terms have largely been abandoned in the medical literature. This change has occurred because the older dichotomous classification did not reflect pathophysiology or outcome. It led to erroneous therapeutic decisions, i.e. treat "primary" pulmonary hypertension only. This in turn led to therapeutic nihilism for many patients labeled "secondary" pulmonary hypertension, and could have contributed to their deaths. The term "primary pulmonary hypertension" has now been replaced with "idiopathic pulmonary arterial hypertension". The terms "primary" and "secondary" pulmonary hypertension should not be used any longer. Further details are in the Classification section below. In medicine, pulmonary hypertension (PH) is an increase in blood pressure in the pulmonary artery or lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion. ...

Signs and symptoms

A history usually reveals gradual onset of shortness of breath, fatigue, non-productive cough, angina pectoris, fainting or syncope, peripheral edema (swelling of the limbs, especially around the ankles and feet), and rarely hemoptysis (coughing up blood). Pulmonary arterial hypertension (PAH) typically does not present with orthopnea or paroxysmal nocturnal dyspnea, while pulmonary venous hypertension typically does. Dyspnea (Latin dyspnoea, Greek dyspnoia from dyspnoos - short of breath) or shortness of breath (SOB) is perceived difficulty breathing or pain on breathing. ... The word fatigue is used in everyday living to describe a range of afflictions, varying from a general state of lethargy to a specific work induced burning sensation within muscle. ... It has been suggested that Central Ischaemic Response be merged into this article or section. ... Edema (BE: oedema, formerly known as dropsy) is swelling of any organ or tissue due to accumulation of excess fluid. ... Hemoptysis (US English) or haemoptysis (International English) is the expectoration (coughing up) of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs (e. ... orthopnea ... Paroxysmal nocturnal dyspnea (PND) is a medical symptom wherein people with congestive heart failure develop difficulties breathing after laying flat. ...

In order to establish the cause, the physician will generally conduct a thorough medical history. A detailed family history is taken to determine whether the disease might be familial. A history of exposure to cocaine, methamphetamine, alcohol leading to cirrhosis, and smoking leading to emphysema are considered significant. Physical examination is performed to look for typical signs of pulmonary hypertension including a loud P2 (pulmonic valve closure sound), (para)sternal heave, jugular venous distension, pedal edema, ascites, hepatojugular reflux, clubbing etc. Physical examination evidence of tricuspid insufficiency is also sought and, if present, is consistent with the presence of pulmonary hypertension. Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. ... This article is about the psychostimulant, d-methamphetamine. ... This article does not cite any references or sources. ... Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrotic scar tissue as well as regenerative nodules, leading to progressive loss of liver function. ... In medicine, the physical examination or clinical examination is the process by which the physician investigates the body of a patient for signs of disease. ... This page is about the condition called edema. ... This article needs to be wikified. ... Clubbing is also used to refer to the activity of gathering socially at nightclubs. ... Tricuspid insufficiency, also termed Tricuspid regurgitation, refers to the failure of the hearts tricuspid valve to close properly during systole. ...

Causes

The most common cause of pulmonary hypertension is left heart failure leading to pulmonary venous hypertension (WHO Group II). This may be due to systolic or diastolic malfunction of the left ventricle or due to valvular dysfunction such as mitral regurgitation, mitral stenosis, aortic stenosis, or aortic regurgitation. It usually manifests as pulmonary edema or pleural effusions. Because the malfunctioning heart does not pump efficiently, blood fails to leave the pulmonary circulation in a timely manner, leading to abnormally high pressure in the pulmonary veins.^[2] The increased pressure in the pulmonary veins can be transmitted back to the pulmonary arteries.^[2] In medicine, pulmonary hypertension (PH) is an increase in blood pressure in the pulmonary artery or lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion. ... Ventricular systole The parts of a QRS complex. ... Diastolic is the adjective form of diastole referring to relaxation of the heart, between muscle contractions. ... In the heart, a ventricle is a heart chamber which collects blood from an atrium (another heart chamber that is smaller than a ventricle) and pumps it out of the heart. ... Mitral regurgitation (MR), also known as mitral insufficiency, is the abnormal leaking of blood through the mitral valve, from the left ventricle into the left atrium of the heart. ... Mitral stenosis is a narrowing of the orifice of the mitral valve of the heart. ... Aortic valve stenosis (AS) is a heart condition caused by the incomplete opening of the aortic valve. ... Aortic insufficiency (AI), also known as aortic regurgitation (AR), is the leaking of the aortic valve of the heart that causes blood to flow in the reverse direction during ventricular diastole, from the aorta into the left ventricle. ... Pulmonary edema is swelling and/or fluid accumulation in the lungs. ... Pleural effusion Chest x-ray of a pleural effusion. ... Pulmonary circulation is the 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. ... The pulmonary veins carry oxygen-rich blood from the lungs to the left atrium of the heart. ...

Common causes of pulmonary arterial hypertension (PAH, WHO Group I) include HIV, scleroderma and other autoimmune disorders, cirrhosis and portal hypertension, sickle cell disease,^[3] congenital heart disease, and others. Use of weight loss pills such as Fen-Phen, Aminorex, fenfluramine (Pondimin), and phentermine led to the development of PAH in the past.^[4] Species Human immunodeficiency virus 1 Human immunodeficiency virus 2 Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS, a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections). ... Scleroderma is a rare, chronic disease characterized by excessive deposits of collagen in the skin or other organs. ... Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ... Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrotic scar tissue as well as regenerative nodules, leading to progressive loss of liver function. ... In medicine, portal hypertension is hypertension (high blood pressure) in the portal vein and its branches. ... ... Cross-section diagram of a normal human heart. ... Fen-phen was an anti-obesity medication (an anorectic) which consisted of two drugs: fenfluramine and phentermine. ... Aminorex is an anorectic stimulant drug of the 2-Amino-5-Aryloxazoline class. ... Fenfluramine is a drug that was part of the Fen-Phen anti-obesity medication (the other drug being phentermine). ... Phentermine is an appetite suppressant of the amphetamine and phenethylamine class. ...

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.^[5] Recent studies have been unable to find an association between human herpesvirus 8 and idiopathic pulmonary arterial hypertension. Kaposis sarcoma-associated herpesvirus (KSHV) is the eighth human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses is HHV-8. ...

When a family history exists, the disease is termed familial pulmonary arterial hypertension (FPAH). IPAH and FPAH are now considered to be genetic disorders linked to mutations in the BMPR2 gene, which encodes a receptor for bone morphogenetic proteins,^[6] as well as the 5-HT(2B) gene, which codes for a serotonin receptor.^[7]. There seems to be an association of idiopathic PAH (not only PAH caused by heart malformations) and Trisomy 21. A genetic disorder is a disease caused by abnormalities in genes or chromosomes. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... Serotonin (pronounced ) (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system (CNS) and enterochromaffin cells in the gastrointestinal tract of animals including humans. ... A child with Down syndrome Down syndrome (also called Downs syndrome) encompasses a number of genetic disorders, of which trisomy 21 (a nondisjunction) is the most representative, causing highly variable degrees of learning difficulties and physical disabilities. ...

Pulmonary embolism also leads to pulmonary hypertension, acutely as well as chronically (WHO Group IV). Treatments for these two conditions are vastly different. Schistosomiasis is a very common cause of pulmonary hypertension in endemic areas such as the Nile river due to obstruction of pulmonary vessels with the parasite. In medicine, pulmonary hypertension (PH) is an increase in blood pressure in the pulmonary artery or lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion. ... Schistosomiasis or bilharzia is a disease affecting many people in developing countries. ... The Nile (Arabic: , transliteration: , Ancient Egyptian iteru, Coptic piaro or phiaro) is a major north-flowing river in Africa, generally regarded as the longest river in the world. ...

Lung diseases that lower oxygen in the blood (hypoxia) are well known causes of pulmonary hypertension (WHO Group III), including COPD, interstitial lung disease such as IPF, Pickwickian syndrome or obesity-hypoventilation syndrome, and possibly sleep apnea. Hypoxia is a pathological condition in which the body as a whole (generalised hypoxia) or region of the body (tissue hypoxia) is deprived of adequate oxygen supply. ... In medicine, pulmonary hypertension (PH) is an increase in blood pressure in the pulmonary artery or lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion. ... Chronic obstructive pulmonary disease (COPD), also known as chronic obstructive airway disease (COAD), is a group of diseases characterized by limitation of airflow in the airway that is not fully reversible. ... Interstitial lung disease (ILD), also known as diffuse parenchymal lung disease (DPLD), refers to a group of lung diseases (including idiopathic pulmonary fibrosis), affecting the alveolar epithelium, pulmonary capillary endothelium, basement membrane, perivascular and perilymphatic tissues. ... Idiopathic pulmonary fibrosis involves scarring of the lung. ... The Pickwickian syndrome, also known as obesity hypoventilation syndrome, is the combination of severe obesity and hypoventilation. ... Sleep apnea, sleep apnoea or sleep apnœa is a sleep disorder characterized by pauses in breathing during sleep. ...

Other causes include sarcoidosis, histiocytosis X, and fibrosing mediastinitis (WHO Group V). Though histiocytosis can refer to any of several specific diseases, the term is generally used to refer to a rare blood disease that is caused by an excess of white blood cells called histiocytes. ... In medicine, pulmonary hypertension (PH) is an increase in blood pressure in the pulmonary artery or lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion. ...

When none of these causes can be found, the disease is termed idiopathic pulmonary arterial hypertension (IPAH). There appears to be a link between IPAH and thyroid diseases,^[8] but this is not regarded as causative.

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 fibrosis. This further increases the blood pressure within the lungs and impairs their blood flow. In addition, the increased workload of the heart causes thickening and enlargement of the right ventricle, making the heart less able to pump blood through the lungs, causing right heart failure. 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. In medicine, pulmonary hypertension (PH) is an increase in blood pressure in the pulmonary artery or lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion. ... Vasoconstriction is the constriction of blood vessels, in other words, when the lumen narrows. ... The heart and lungs (from an older edition of Grays Anatomy) The lung is an organ belonging to the respiratory system and interfacing to the circulatory system of air-breathing vertebrates. ... Fibrosis is the formation or development of excess fibrous connective tissue in an organ or tissue as a reparative or reactive process, as opposed to a formation of fibrous tissue as a normal constituent of an organ or tissue. ... The right ventricle is one of four chambers (two atria and two ventricles) in the human heart. ... General Name, symbol, number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, period, block 16, 2, p Appearance colorless (gas) pale blue (liquid) Standard atomic weight 15. ...

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 pumps blood efficiently, leading to pooling of blood in the lungs. This causes pulmonary edema and pleural effusions. In medicine, pulmonary hypertension (PH) is an increase in blood pressure in the pulmonary artery or lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion. ... Pulmonary edema is swelling and/or fluid accumulation in the lungs. ... Pleural effusion Chest x-ray of a pleural effusion. ...

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 medicine, pulmonary hypertension (PH) is an increase in blood pressure in the pulmonary artery or lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion. ... The blood vessels are part of the circulatory system and function to transport blood throughout the body. ... Pathophysiology is the study of the disturbance of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from a disease or abnormal syndrome or condition that may not qualify to be called a disease. ...

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. In medicine, pulmonary hypertension (PH) is an increase in blood pressure in the pulmonary artery or lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion. ... Pathophysiology is the study of the disturbance of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from a disease or abnormal syndrome or condition that may not qualify to be called a disease. ...

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, thomboembolic, or miscellaneous varieties.

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. In medicine, the physical examination or clinical examination is the process by which the physician investigates the body of a patient for signs of disease. ... Front of thorax, showing surface relations of bones, lungs (purple), pleura (blue), and heart (red outline). ... The pulmonary valve, also known as pulmonic valve, is the semilunar valve of the heart that lies between the right ventricle and the pulmonary artery and has three cusps. ... The jugular venous pressure (JVP, sometimes referred to as jugular venous pulse) is the indirectly observed pressure over the venous system. ... Peripheral edema ... This article needs to be wikified. ... Clubbing is also used to refer to the activity of gathering socially at nightclubs. ...

Further procedures are required to confirm the presence of pulmonary hypertension and exclude other possible diagnoses. These generally include pulmonary function tests, blood tests to exclude HIV, autoimmune diseases, and liver disease, electrocardiography (ECG), arterial blood gas measurements, X-rays 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. Spirometry, also known as Pulmonary Function Testing (PFT), is the measurement of lung function, specifically by measuring the volume and speed of air that can be inhaled and exhaled. ... Blood tests are laboratory tests done on blood to gain an appreciation of disease states and the function of organs. ... Species Human immunodeficiency virus 1 Human immunodeficiency virus 2 Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS, a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections). ... Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ... ECG may also refer to the East Coast Greenway Lead II An Electrocardiogram (ECG or EKG, abbreviated from the German Elektrokardiogramm) is a graphic produced by an electrocardiograph, which records the electrical voltage in the heart in the form of a continuous strip graph. ... Arterial blood gas measurement is a blood test that is performed to determine the concentration of oxygen, carbon dioxide and bicarbonate, as well as the pH, in the blood. ... In the NATO phonetic alphabet, X-ray represents the letter X. An X-ray picture (radiograph) taken by Röntgen An X-ray is a form of electromagnetic radiation with a wavelength approximately in the range of 5 pm to 10 nanometers (corresponding to frequencies in the range 30 PHz... CAT apparatus in a hospital Computed axial tomography (CAT), computer-assisted tomography, computed tomography, CT, or body section roentgenography is the process of using digital processing to generate a three-dimensional image of the internals of an object from a large series of two-dimensional X-ray images taken around... Interstitial lung disease (ILD), also known as diffuse parenchymal lung disease (DPLD), refers to a group of lung diseases (including idiopathic pulmonary fibrosis), affecting the alveolar epithelium, pulmonary capillary endothelium, basement membrane, perivascular and perilymphatic tissues. ... A ventilation/perfusion scan, also called a V/Q scan, is a medical test to measure the circulation of air and blood within a patients lungs. ... Brain natriuretic peptide (also 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 myocytes (heart muscles cells) in the ventricles. ...

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. An echocardiogram. ... In medicine pulmonary artery catheterization is the insertion of a catheter into a pulmonary artery. ... An echocardiogram. ... Cardiac catheterization (heart cath) is the insertion of a catheter into a chamber or vessel of the heart. ... In medicine pulmonary artery catheterization is the insertion of a catheter into a pulmonary artery. ... Cardiac output (CO) is the volume of blood being pumped by the heart, in particular by a ventricle in a minute. ...

Normal pulmonary arterial pressure in a person living at sea level has a mean value of 12–16 mm Hg (1600–2100 Pa). Definite pulmonary hypertension is present when mean pressures at rest exceed 25 mm Hg (3300 Pa). If mean pulmonary artery pressure rises above 30 mm Hg (4000 Pa) with exercise, that is also considered pulmonary hypertension.

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 more than 25 mm Hg. Roughly, mPAP = 0.61•sPAP + 2. The echocardiogram is an ultrasound of the heart. ...

Classification

Current classification

In 2003, the 3rd World Symposium on Pulmonary Arterial Hypertension was convened in Venice to modify the classification based on the new understanding 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:^[9]

• WHO Group I - Pulmonary arterial hypertension (PAH)
• WHO Group II - Pulmonary hypertension associated with left heart disease
• WHO Group III - Pulmonary hypertension associated with lung diseases and/or hypoxemia
• WHO Group IV - Pulmonary hypertension due to chronic thrombotic and/or embolic disease
• WHO Group V - Miscellaneous

Previous terminology

The terms primary and secondary pulmonary hypertension (PPH and SPH) were formerly used to classify the disease. This led to the assumption that only the primary disease should be treated, and the secondary variety should be ignored in favor of treating only the underlying illness. In fact all forms of pulmonary arterial hypertension are treatable. Unfortunately, this classification system still persists in the minds of many physicians, and probably leads to many patients with being denied treatment. This approach to pulmonary arterial hypertension may also contribute to underdiagnosis. It is estimated that there are about 100,000 patients with PAH in the US, but only 15-20,000 have been diagnosed. Many others have been misdiagnosed as COPD, asthma, or congestive heart failure. Chronic obstructive pulmonary disease (COPD), also known as chronic obstructive airway disease (COAD), is a group of diseases characterized by limitation of airflow in the airway that is not fully reversible. ... Congestive heart failure (CHF), also called congestive cardiac failure (CCF) or just heart failure, is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood throughout the body. ...

The term primary pulmonary hypertension (PPH) has now been replaced with idiopathic pulmonary arterial hypertension (IPAH) in much of the medical literature. However, some physicians continue to use the older classification inappropriately.

Familial pulmonary arterial hypertension (FPAH) and pulmonary arterial hypertension associated with anorexigens such as Fen-Phen also used to be called PPH, and now are a subcategory of PAH. Fen-phen was an anti-obesity medication (an anorectic) which consisted of two drugs: fenfluramine and phentermine. ...

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. Women are almost three times as likely to present with IPAH than men.

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%. Scleroderma is a rare, chronic disease characterized by excessive deposits of collagen in the skin or other organs. ... Rheumatoid arthritis (RA) is traditionally considered a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. ... In medicine, portal hypertension is hypertension (high blood pressure) in the portal vein and its branches. ...

Diet pills such as Fen-Phen produced an annual incidence of 25-50 per million per year. Fen-phen was an anti-obesity medication (an anorectic) which consisted of two drugs: fenfluramine and phentermine. ...

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 or obesity-hypoventilation syndrome is very commonly associated with right heart failure due to pulmonary hypertension. Chronic obstructive pulmonary disease (COPD), also known as chronic obstructive airway disease (COAD), is a group of diseases characterized by limitation of airflow in the airway that is not fully reversible. ... The Pickwickian syndrome, also known as obesity hypoventilation syndrome, is the combination of severe obesity and hypoventilation. ...

Treatment

Treatment is determined by whether the PH is arterial, venous, hypoxic, thromboembolic, or miscellaneous. Since pulmonary venous hypertension is synonymous with congestive heart failure, the treatment is to optimize left ventricular function by the use of diuretics, beta blockers, ACE inhibitors, etc., or to repair/replace the mitral valve or aortic valve. Congestive heart failure (CHF), also called congestive cardiac failure (CCF) or just heart failure, is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood throughout the body. ... This illustration shows where some types of diuretics act, and what they do. ... Beta blockers or beta-adrenergic blocking agents are a class of drugs used to treat a variety of cardiovascular conditions and some other diseases. ... Captopril, the first ACE inhibitor ACE inhibitors, or inhibitors of Angiotensin-Converting Enzyme, are a group of pharmaceuticals that are used primarily in treatment of hypertension and congestive heart failure, in most cases as the drugs of first choice. ... The mitral valve (also known as the bicuspid valve or left atrioventricular valve), is a dual flap (bi = 2) valve in the heart that lies between the left atrium (LA) and the left ventricle (LV). ... The aortic valve is one of the valves of the heart. ...

In PAH, lifestyle changes, digoxin, diuretics, oral anticoagulants, and oxygen therapy are considered conventional therapy, but have never been proven to be beneficial in a randomized, prospective manner. Digoxin (INN) (IPA: ) is a purified cardiac glycoside extracted from the foxglove plant, Digitalis lanata. ... This illustration shows where some types of diuretics act, and what they do. ... An anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting. ...

High dose calcium channel blockers 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 blockers in the long term. Calcium channel blockers are a class of drugs and natural substances with effects on many excitable cells of the body, like the muscle of the heart, smooth muscles of the vessels or neuron cells. ... In medicine pulmonary artery catheterization is the insertion of a catheter into a pulmonary artery. ... Adenosine is a nucleoside composed of adenine attached to a ribose (ribofuranose) moiety via a β-N9-glycosidic bond. ... Prostacyclin is a member of the family of lipid molecules known as eicosanoids. ... R-phrases , , , , S-phrases , , , Except where noted otherwise, data are given for materials in their standard state (at 25 Â°C, 100 kPa) Infobox disclaimer and references Nitric oxide or Nitrogen monoxide is a chemical compound with chemical formula NO. This gas is an important signaling molecule in the body of... Calcium channel blockers are a class of drugs and natural substances with effects on many excitable cells of the body, like the muscle of the heart, smooth muscles of the vessels or neuron cells. ...

Vasoactive substances

Many pathways are involved in the abnormal proliferation and contraction of the smooth-muscle 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 antagonists, phosphodiesterase type 5 inhibitors, and prostacyclin derivatives. A endothelin receptor antagonist (ERA) is a drug which blocks endothelin receptors. ... A phosphodiesterase (PDE) is an enzyme that catalyzes the hydrolysis of phosphodiester bonds. ...

Prostaglandins

Prostacyclin (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 prostanoids 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®) is the only inhaled form of prostacyclin approved for use in the US and Europe. This form of administration has the advantage of selective deposition in the lungs with less systemic side effects. Oral and inhaled forms of Remodulin® are under development. Beraprost is an oral prostanoid available in Japan and South Korea. Prostacyclin is a member of the family of lipid molecules known as eicosanoids. ... E1 - Alprostadil I2 - Prostacyclin 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. ... Prostacyclin is a member of the family of lipid molecules known as eicosanoids. ... Prostacyclin is a member of the family of lipid molecules known as eicosanoids. ... In medicine, a central venous catheter (CVC or central venous line) is a catheter placed into a large vein in the neck, chest or groin, this is inserted by a physician when the patient needs more intensive cardiovascular monitoring, for assessment of fluid status, and for increased viability of intravenous... Sepsis (in Greek Σήψις, putrefaction) is a serious medical condition, resulting from the immune response to a severe infection. ... Thrombosis is the formation of a clot or thrombus inside a blood vessel, obstructing the flow of blood through the circulatory system. ... Prostanoid is the term used to describe three classes of eicosanoids: the prostaglandins (mediators of inflammatory and anaphylactic reactions), the thromboxanes (mediators of vasoconstriction) and the prostacyclins (active in the resolution phase of inflamation. ... Trepostinil is a synthetic analogue of prostacyclin, used to treat pulmonary hypertension. ... The Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, is recognized as the leading United States agency for protecting the public health and safety of people. ... iloprost, an inhalation solution, is sold under the name Ventavis® and is used to treat pulmonary arterial hypertension (PAH). ... iloprost, an inhalation solution, is sold under the name Ventavis® and is used to treat pulmonary arterial hypertension (PAH). ... Beraprost is a synthetic analogue of prostacyclin, under clinical trials for the treatment of pulmonary hypertension. ...

Endothelin receptor antagonists

The dual (ET_A and ET_B) endothelin receptor antagonist bosentan (marketed as Tracleer®) was approved in 2001. Sitaxsentan, a selective endothelin receptor antagonist that blocks only the action of ET_A, has been approved for use in Canada, Australia, and the European Union, to be marketed under the name Thelin®.^[10] Sitaxsentan has not been approved for marketing by the US FDA. A new trial to address FDA's concerns will begin in 2008. A similar drug, ambrisentan is marketed as Letairis® in U.S. by Gilead Sciences.^[11] In addition, another dual/nonselective endothelin antagonist, Actelion-1, from the makers of Tracleer®, will enter clinical trials in 2008. Endothelin is a 21-amino acid vasoconstricting peptide that plays a key part in vascular homeostasis. ... Bosentan is a dual endothelin receptor antagonist important in the treatment of pulmonary artery hypertension (PAH). ... Sitaxsentan or sitaxsentan sodium (to be marketed as Thelin®) is a small molecule sodium salt that blocks the action of endothelin on the endothelin-A receptor selectively (by a factor of 6000 compared to the ERB), and is undergoing FDA approval for treating pulmonary hypertension. ... Ambrisentan is a drug being researched for use in the treatment of pulmonary hypertension. ... Gilead Sciences NASDAQ: GILD is a biopharmaceutical company that discovers, develops and commercializes therapeutics to advance the care of patients suffering from life-threatening diseases, principally HIV, hepatitis B and influenza. ...

Phosphodiesterase type 5 inhibitors

Sildenafil, a selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5), was approved for the treatment of PAH in 2005. It is marketed for PAH as Revatio®. Tadalafil (currently marketed as Cialis® for erectile dysfunction) is currently finishing its Phase III clinical trials and results should be reported very soon. Sildenafil citrate, sold under the names Viagra, Revatio and generically under various other names, is a drug used to treat male erectile dysfunction (impotence) and pulmonary arterial hypertension (PAH), developed by the pharmaceutical company Pfizer. ... cGMP specific phosphodiesterase type 5 is an enzyme (EC 3. ... Year 2005 (MMV) was a common year starting on Saturday (link displays full calendar) of the Gregorian calendar. ... Tadalafil is a drug used to treat male erectile dysfunction (impotence). ... Erectile dysfunction (ED) or impotence is a sexual dysfunction characterized by the inability to develop or maintain an erection of the penis. ... In health care, including medicine, a clinical trial (synonyms: clinical studies, research protocols, medical research) is a process in which a medicine or other medical treatment is tested for its safety and effectiveness, often in comparison to existing treatments. ...

Other agents

Vasoactive intestinal peptide by inhalation should enter clinical trials for PAH in 2008. PRX-08066 is a serotonin antagonist currently being developed for hypoxic pulmonary hypertension. A recent study showed benefit as measured by echocardiography. A study using cardiac catheterization with a Swan-Ganz catheter is underway. VIP is a peptide hormone containing 28 amino acid residues. ... Cardiac catheterization (heart cath) is the insertion of a catheter into a chamber or vessel of the heart. ... In medicine pulmonary artery catheterization is the insertion of a catheter into a pulmonary artery. ...

Surgical

Atrial septostomy 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). It is best performed in experienced centers. 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.^[12] In anatomy, the atrium (plural: atria) refers to a chamber or space. ... In probability theory and statistics, a median is a type of average that is described as the number dividing the higher half of a sample, a population, or a probability distribution, from the lower half. ...

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 large and very difficult procedure that is currently performed in a few select centers. Case series show remarkable success in most patients. In thoracic surgery, a pulmonary thromboendarterectomy, PTE, is an operation that removes organized clotted blood (thrombus) from the pulmonary arteries. ... For Trombe wall (used in solar homes), see Trombe wall. ...

Treatment 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.

Prognosis

The NIH IPAH registry from the 1980's showed an untreated median survival of 2-3 years from time of diagnosis, with the cause of death usually being right ventricular failure (cor pulmonale). 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.^[13] 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.^[14] Cor pulmonale, also known as right heart failure, is a medical term used to describe a change in structure and function of the right ventricle of the heart as a result of a respiratory disorder. ...

References

is the 150th day of the year (151st in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 189th day of the year (190th in leap years) in the Gregorian calendar. ... Gilead Sciences NASDAQ: GILD is a biopharmaceutical company that discovers, develops and commercializes therapeutics to advance the care of patients suffering from life-threatening diseases, principally HIV, hepatitis B and influenza. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 166th day of the year (167th in leap years) in the Gregorian calendar. ... For information on Wikipedia press releases, see Wikipedia:Press releases. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 167th day of the year (168th in leap years) in the Gregorian calendar. ... is the 121st day of the year (122nd in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 87th day of the year (88th in leap years) in the Gregorian calendar. ...

External links

• The Merck Manual of Diagnosis and Therapy: Pulmonary Hypertension
• The Pulmonary Hypertension Association
• PH Central - the internet resource for Pulmonary Arterial Hypertension
• Facts About Primary Pulmonary Hypertension from the National Heart, Lung, and Blood Institute (NHLBI)
• Webcast: The Changing World of Pulmonary Arterial Hypertension Therapies - American College of CHEST Physicians
• pph at NIH/UW GeneTests - "BMPR2-Related Primary Pulmonary Hypertension"