History

Fact Explanation
Reduced exercise tolerance or unusual fatigue [5] [7] As there's hypoxaemia, aerobic regeneration of ATP is impaired, with more work being done anaerobically. Because the mechanism of anaerobic ATP regeneration stimulates anaerobic glycolysis, lactic acidosis results causing muscle fatigue [6]
Shortness of breath [5] [7] Shortness of breath during exercise can be related to the relative hypoperfusion of their well-ventilated alveoli (increased dead space). In normal subjects, the ventilatory response (V̇e) to exercise is related to CO2 output (V̇co2)In this, the ventilation of under perfused alveoli causes an increase in dead space ventilation, manifested by a hyperbolic increase in V̇e relative to the V̇co2 increase during exercise.As well as the lactic acidosis and hypoxemia can act as stimuli to breathing which causes the sensation of dyspnoea [6]
Chest pain [5] [7] Can be due to shortness of breath as well as ultimate right heart failure [6]
Loss of consciousness (or near-fainting episodes) [5] [7] This is due to inability maintain cardiac output and systemic blood pressure with exercise and/or sudden arterial hypoxemia via a patent foramen ovale.[6]
Ankle swelling [5] [7] Persistent pulmonary hypertension causes right ventricular failure which exerts the pressure on right atrium and ultimate right heart failure [1] [2] [3] [4]
References
  1. TAN X, YANG W, GUO J, ZHANG Y, WU C, SAPKOTA R, KUSHWAHA SP, GONG S, SUN X, LIU J. Usefulness of Decrease in Oxygen Uptake Efficiency to Identify Gas Exchange Abnormality in Patients with Idiopathic Pulmonary Arterial Hypertension PLoS One [online] , 9(6):e98889 [viewed 20 June 2014] Available from: doi:10.1371/journal.pone.0098889
  2. LIU XD, GUO SY, YANG LL, ZHANG XL, FU WY, WANG XF. Anti-endothelial cell antibodies in connective tissue diseases associated with pulmonary arterial hypertension J Thorac Dis [online] 2014 May, 6(5):497-502 [viewed 20 June 2014] Available from: doi:10.3978/j.issn.2072-1439.2014.03.27
  3. TAKATSUKI S, IVY DD. Current Challenges in Pediatric Pulmonary Hypertension Semin Respir Crit Care Med [online] 2013 Oct, 34(5):627-644 [viewed 20 June 2014] Available from: doi:10.1055/s-0033-1356461
  4. SEFERIAN A., SIMONNEAU G.. Therapies for pulmonary arterial hypertension: where are we today, where do we go tomorrow?. European Respiratory Review [online] December, 22(129):217-226 [viewed 20 June 2014] Available from: doi:10.1183/09059180.00001713
  5. BENISTY J. I.. Pulmonary Hypertension. [online] 2002 December, 106(24):192e-194 [viewed 20 June 2014] Available from: doi:10.1161/​01.CIR.0000042762.47822.FE
  6. SUN X.-G., HANSEN J. E., OUDIZ R. J., WASSERMAN K.. Exercise Pathophysiology in Patients With Primary Pulmonary Hypertension. Circulation [online] 2001 July, 104(4):429-435 [viewed 20 June 2014] Available from: doi:10.1161/​hc2901.093198
  7. MCGOON MICHAEL. Screening, Early Detection, and Diagnosis of Pulmonary Arterial Hypertension . Chest [online] 2004 July [viewed 20 June 2014] Available from: doi:10.1378/chest.126.1_suppl.14S

Examination

Fact Explanation
Palpable second heart sound in the pulmonary area [1] [2] [3] This is present in >90% and reflects increased force of pulmonary valve closure due to elevated pulmonary artery pressure and the pulmonary component is augmented. [1]
Right ventricular heave [1] [2] [3] Due to impulse of the hypertrophied high-pressure right ventricle [1]
Loud second heart sound (Pulmonary component) in the pulmonary area [1] [2] [3] Due to increased force of pulmonary valve closure due to elevated pulmonary artery pressure and the pulmonary component is augmented [1]
Paradoxical splitting of the second heart sound [4] Abnormally close splitting of the second heart sound, widely regarded as a sign of pulmonary hypertension is thought to be due to high intensity of the pulmonary heart sound relative to the aortic heart sound [4]
early systolic ejection click [1] [2] Due to sudden interruption of pulmonary valve opening [1]
midsystolic ejection murmur [1] [2] This is a caused by turbulent transvalvular pulmonary flow [1]
S4 gallop rhythm [1] [2] Due to right ventricular hypertrophy [1]
Elevated jugular venous pulsations and large a waves [1] [2] Due to high right ventricular filling pressure [1]
Diastolic murmur (Pulmonary regurgitation murmer (Graham Steell murmur) [1] [2] Due to increased blood flow which flows back to right ventricle [1]
Holosystolic murmur of tricuspid regurgitation [1] [2] Due to increased blood flow via tricuspid valve and audible at the lower left sternal border and increased with inspiration[1]
right ventricular S3 gallop [1] [2] This is audible in 23% and is a sign of advanced disease [1]
Elevated jugular venous pressure with accentuated V waves [1] [2] [3] Due to tricuspid regurgitation and is a sign of advanced disease [1]
Hepatomegaly with pulsatile liver with hepatojugular reflux [1][2] Due to tricuspid regurgitation and is a sign of advanced disease [1]
peripheral edema [1] [2] [3] Due to right ventricular failure which results with prolonged pulmonary hypertension [1]
Ascitis [1] [2] [3] Due to right ventricular failure which results with prolonged pulmonary hypertension [1]
Low BP, diminished pulse pressure, and cool extremities [1] [2] Due to markedly reduced cardiac out put leading to cardiogenic shock [1]
cyanosis [1] [2] Due to ight-to-left shunting, severely reduced cardiac output, or severe impairment in intrapulmonary gas transfer. this is seen in 20% of patients [1]
References
  1. MCGOON MICHAEL. Screening, Early Detection, and Diagnosis of Pulmonary Arterial Hypertension . Chest [online] 2004 July [viewed 20 June 2014] Available from: doi:10.1378/chest.126.1_suppl.14S
  2. GALIE N, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). European Heart Journal [online] December, 30(20):2493-2537 [viewed 20 June 2014] Available from: doi:10.1093/eurheartj/ehp297
  3. BARST ROBYN J, MCGOON MICHAEL, TORBICKI ADAM, SITBON OLIVIER, KROWKA MICHAEL J, OLSCHEWSKI HORST, GAINE SEAN. Diagnosis and differential assessment of pulmonary arterial hypertension. Journal of the American College of Cardiology [online] 2004 June, 43(12):S40-S47 [viewed 20 June 2014] Available from: doi:10.1016/j.jacc.2004.02.032
  4. SUTTON G, HARRIS A, LEATHAM A. Second heart sound in pulmonary hypertension. Br Heart J [online] 1968 Nov, 30(6):743-756 [viewed 21 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC487797

Differential Diagnoses

Fact Explanation
Chronic pulmonary thromboembolism [1] In this thrombi attached to the proximal arteries narrow their lumen size and cause stiffening of the arterial wall. Narrowing the arteries would result in increased resistance of the proximal arteries [1]
Secondary Pulmonary Hypertension [2] In this entity pulmonary hypertension develops secondary to left-sided cardiac valvular disease, myocardial disease, congenital heart disease, and any clinically important respiratory, connective-tissue, or chronic thromboembolic diseases [2] [3]
Portal hypertension [2] Portopulmonary hypertension (PPHTN) is a known but a rare severe complication of cirrhosis and involves endothelial and smooth muscle proliferation, and features are similar to plexogenic arteriopathy of Idiopathic Pulmonary Hypertension [4]
Systemic sclerosis and mixed connective tissue disorders [5] Systemic sclerosis (SS) is a systemic autoimmune disease which causes vascular lesions and fibrosis of skin, lungs, heart, intestinal tract, joints, and muscles. Lung involvement with Interstitial lung disease (ILD) is diagnosed in patients [5]
Systemic Lupus Erythematosus [6] Systemic lupus erythematosus (SLE) is a multi systemic disease characterized by the production of a wide array of autoantibodies. The involvement of the lung and pulmonary fibrosis is seen [6]
Dilated cardiomyopathy [7] Dilated cardiomyopathy (DCM) in which there's dilatation of ventricles can be developed from alcohol drinking, pregnancy, chronic uncontrolled tachycardia, hypothyroidism, hyperthyroidism, drug use and other endocrine dysfunctions and clinical features similar to pulmonary hypertension is seen [7]
Mitral stenosis [8] Right ventricular (RV) dysfunction can occur in isolated severe mitral stenosis (MS) in which the diameter of the mitral vavle is small. Clinical features are similar to pulmonary hypertension [8]
References
  1. NAKAYAMA YASUNORI, NAKANISHI NORIFUMI, SUGIMACHI MASARU, TAKAKI HIROSHI, KYOTANI SHINGO, SATOH TORU, OKANO YOSHIAKI, KUNIEDA TAKEYOSHI, SUNAGAWA KENJI. Characteristics of Pulmonary Artery Pressure Waveform for Differential Diagnosis of Chronic Pulmonary Thromboembolism and Primary Pulmonary Hypertension. Journal of the American College of Cardiology [online] 1997 May, 29(6):1311-1316 [viewed 20 June 2014] Available from: doi:10.1016/S0735-1097(97)00054-5
  2. RUBIN LEWIS J.. Primary Pulmonary Hypertension. N Engl J Med [online] 1997 January, 336(2):111-117 [viewed 20 June 2014] Available from: doi:10.1056/NEJM199701093360207
  3. MCGOON MICHAEL. Screening, Early Detection, and Diagnosis of Pulmonary Arterial Hypertension . Chest [online] 2004 July [viewed 20 June 2014] Available from: doi:10.1378/chest.126.1_suppl.14S
  4. MANCUSO L, SCORDATO F, PIERI M, VALERIO E, MANCUSO A. Management of portopulmonary hypertension: New perspectives World J Gastroenterol [online] 2013 Dec 7, 19(45):8252-8257 [viewed 20 June 2014] Available from: doi:10.3748/wjg.v19.i45.8252
  5. BHANSING KJ, LAMMENS M, KNAAPEN HK, VAN RIEL PL, VAN ENGELEN BG, VONK MC. Scleroderma-polymyositis overlap syndrome versus idiopathic polymyositis and systemic sclerosis: a descriptive study on clinical features and myopathology Arthritis Res Ther [online] 2014, 16(3):R111 [viewed 20 June 2014] Available from: doi:10.1186/ar4562
  6. MAK A, KOW NY. The Pathology of T Cells in Systemic Lupus Erythematosus J Immunol Res [online] 2014:419029 [viewed 20 June 2014] Available from: doi:10.1155/2014/419029
  7. SEOL MD, LEE YS, KIM DK, CHOI YH, KIM DJ, PARK SH, CHO HJ, CHO WH. Dilated Cardiomyopathy Secondary to Hypothyroidism: Case Report with a Review of Literatures J Cardiovasc Ultrasound [online] 2014 Mar, 22(1):32-35 [viewed 20 June 2014] Available from: doi:10.4250/jcu.2014.22.1.32
  8. KUMAR V, JOSE VJ, PATI PK, JOSE J. Assessment of right ventricular strain and strain rate in patients with severe mitral stenosis before and after balloon mitral valvuloplasty Indian Heart J [online] 2014 Mar, 66(2):176-182 [viewed 20 June 2014] Available from: doi:10.1016/j.ihj.2014.02.012

Investigations - for Diagnosis

Fact Explanation
Chest X-ray [1] The signs which are suggestive of PH are enlarged main and hilar pulmonary arterial shadows, with attenuation of peripheral pulmonary vascular markings (“pruning”). Right ventricular enlargement is seen by impingement of the anteriorly situated right ventricular silhouette into the retrosternal clear space on the lateral CXR. The CXR is also useful in excluding coexistent conditions related to PH, such as pulmonary venous congestion (pulmonary venous hypertension, pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis), hyperinflation (COPD), or kyphosis (restrictive ventilatory disease) [2]
Electrocardiography [1] PAH results in right ventricular hypertrophy and right-heart dilation. These Right ventricular hypertrophy and right-axis deviation on ECG are seen in 87% and 79%, respectively. ECG findings suggestive of PAH are right-axis deviation, a tall R wave and small S wave with R/S ratio less than 1 in lead V1, qR complex in lead V1, rSR’ pattern in lead V1, a large S wave and small R wave with R/S ratio less than 1 in lead V5 or V6; or S1, S2, S3 pattern. ST-T segment wave depression and inversion are often present in the right precordial leads. Right atrial enlargement is manifested as a tall P wave (≥ 2.5 mm) in leads II, III, and aVF and frontal P-axis of ≥ 75° [2] [3]
Echocardiography and Doppler Echocardiography [3] Echocardiography can exclude congenital, valvular, and myocardial disease and provides estimation of pulmonary-artery systolic pressure [3]
Computed tomography and lung scanning [3] The results of ventilation–perfusion scanning can be normal or reveal a patchy distribution in particularly pulmonary veno-occlusive disease, in contrast to the multiple, larger perfusion defects typical of chronic major-vessel thromboembolic pulmonary hypertension [3]
Pulmonary angiography [3] Pulmonary angiography is useful when the perfusion lung scan is inconclusive and can be performed safely even in patients with severe pulmonary hypertension [3]
Cardiac Catheterization [4] This is the investigation of choice to diagnose pulmonary hypertension.The definition is given when pulmonary artery pressure of greater than 25 mm Hg, with a normal pulmonary artery occlusion pressure of 15 mm Hg or less and these are found with cardiac catheterization. Also secondary causes for pulmonary hypertension are excluded, it also shows elevated right atrial pressure, and depressed cardiac output. Pressures on the left side of the heart are usually normal, although extreme dilation of the right heart chambers can compress the left chambers to a degree that limits filling and produces small increases in diastolic pressures. But pulmonary-capillary wedge pressure is usually normal, even in veno-occlusive disease, because of the patency of the larger pulmonary veins and the patchy nature of the disease process in the veins [4] [3]
Antinuclear Antibody [3] This is done to screen for connective-tissue diseases. Positive results of antinuclear-antibody tests are common, usually with a low titer [3]
Cardiopulmonary exercise tests [3] These show altered cardiac function, with reduced maximal oxygen consumption, high minute ventilation, a low anaerobic threshold, reduced maximal oxygen pulse, and an increased alveolar–arterial oxygen gradient. There is a correlation between the distance walked during a six-minute walk test and the severity of pulmonary hypertension [3]
Thyrotropin [2] Thyroid disease is suggested as a risk factor for Pulmonary hypertension. Although it is unclear whether or not thyroid disease is causally related [2]
B-Type Natriuretic Peptide [2] Levels of brain natriuretic peptide, indicative of right ventricular pressure overload, correlate with both severity of right ventricular dysfunction and mortality, therefore has a prognostic value [2]
HIV screening [2] HIV infection is associated with an increased prevalence of PH, upto 0.5%. Therefore possibility of HIV exposure should be assessed with appropriate blood testing in all patients with unexplained pulmonary hypertension [2]
Serum Uric acid level [2] These are often elevated and correlate with mean right atrial pressure [2]
References
  1. BENISTY J. I.. Pulmonary Hypertension. [online] 2002 December, 106(24):192e-194 [viewed 20 June 2014] Available from: doi:10.1161/​01.CIR.0000042762.47822.FE
  2. MCGOON MICHAEL. Screening, Early Detection, and Diagnosis of Pulmonary Arterial Hypertension . Chest [online] 2004 July [viewed 20 June 2014] Available from: doi:10.1378/chest.126.1_suppl.14S
  3. RUBIN LEWIS J.. Primary Pulmonary Hypertension. N Engl J Med [online] 1997 January, 336(2):111-117 [viewed 20 June 2014] Available from: doi:10.1056/NEJM199701093360207
  4. TAKATSUKI S, IVY DD. Current Challenges in Pediatric Pulmonary Hypertension Semin Respir Crit Care Med [online] 2013 Oct, 34(5):627-644 [viewed 20 June 2014] Available from: doi:10.1055/s-0033-1356461

Investigations - Fitness for Management

Fact Explanation
Full blood count [3] This is done to exclude significant anaemia and any quantitative platelet or leukocyte abnormality [3]
Serum Creatinine and Blood urea nitogen, and serum electrolyes [3] As these patients are on chronic diuretic therapy it may produce total-body sodium and potassium depletion, and uraemia. Hypokalaemia is a relatively common finding in cardiac surgical patients. Also to assess renal function [3]
Coagulation profile [3] To exclude any coagulopathy, and also specially since patients are on Warfarin this is important [3]
Chest X-ray [3] This gives information about heart size, pulmonary vasculature, lungs and bony anatomy of the chest [3]
12 lead Electrocardiogram [3] To assess any arrhythmias, right axis deviation, or right ventricular hypertrophy [3]
Echocardiography [3] This is done to define cardiac anatomy and assess ventricular and valvular function. It is non invasive therefore it's useful tool for monitoring disease progression and assisting in determining both the timing and type of surgical intervention and to assess left ventricular function [3]
Lung function tests [1] These are done before lung transplantation and include FVC, FEV1, and single-breath carbon monoxide lung transfer factor (TLco) [1]
Cardiopulmonary exercise testing [1] [2] Cardiopulmonary exercise test was performed where an electrically-braked cycle ergometer was used. Heart rate (HR) and rhythm were monitored with an electrocardiograph. [1]
Cardiac catheterization [1] This is done to evaluate hemodynamic status. A flow-directed pulmonary artery catheter is inserted, using the right femoral vein approach. With this system, mean pulmonary artery wedge (Ppaw), mean pulmonary artery (Ppa), and mean right atrial pressures (Pra ) were recorded along with cardiac output (CO) which is measured with the thermodilution technique and also cardiac index [1]
References
  1. SCHWAIBLMAIR MARTIN, REICHENSPURNER HERMANN, MÜLLER CHRISTIAN, BRIEGEL JOSEF, FÜRST HEINER, GROH JÜRGEN, REICHART BRUNO, VOGELMEIER CLAUS. Cardiopulmonary Exercise Testing Before and After Lung and Heart–Lung Transplantation. Am J Respir Crit Care Med [online] 1999 April, 159(4):1277-1283 [viewed 21 June 2014] Available from: doi:10.1164/ajrccm.159.4.980511
  2. STRUTHERS R., ERASMUS P., HOLMES K., WARMAN P., COLLINGWOOD A., SNEYD J. R.. Assessing fitness for surgery: a comparison of questionnaire, incremental shuttle walk, and cardiopulmonary exercise testing in general surgical patients. British Journal of Anaesthesia [online] December, 101(6):774-780 [viewed 21 June 2014] Available from: doi:10.1093/bja/aen310
  3. CORNELISSEN H.. Preoperative assessment for cardiac surgery. Continuing Education in Anaesthesia, Critical Care & Pain [online] 2006 June, 6(3):109-113 [viewed 21 June 2014] Available from: doi:10.1093/bjaceaccp/mkl013

Investigations - Followup

Fact Explanation
Chest X-ray [1] This shows right ventricular enlargement in advanced disease [2]
Electrocardiography [2] This shows right ventricular hypertrophy and right-axis deviation on ECG. [2] [3]
Echocardiography and Doppler Echocardiography [1] This provides estimation of pulmonary-artery systolic pressure.
Cardiopulmonary exercise tests [3] These show altered cardiac function, with reduced maximal oxygen consumption, high minute ventilation, a low anaerobic threshold, reduced maximal oxygen pulse, and an increased alveolar–arterial oxygen gradient. There is a correlation between the distance walked during a six-minute walk test and the severity of pulmonary hypertension [3]
B-Type Natriuretic Peptide [2] Levels of brain natriuretic peptide, indicative of right ventricular pressure overload, correlate with both severity of right ventricular dysfunction and mortality, therefore has a prognostic value [2]
Serum Uric acid level [2] These are often elevated and correlate with mean right atrial pressure [2]
References
  1. BENISTY J. I.. Pulmonary Hypertension. [online] 2002 December, 106(24):192e-194 [viewed 20 June 2014] Available from: doi:10.1161/01.CIR.0000042762.47822.FE
  2. MCGOON MICHAEL. Screening, Early Detection, and Diagnosis of Pulmonary Arterial Hypertension . Chest [online] 2004 July [viewed 20 June 2014] Available from: doi:10.1378/chest.126.1_suppl.14S
  3. RUBIN LEWIS J.. Primary Pulmonary Hypertension. N Engl J Med [online] 1997 January, 336(2):111-117 [viewed 20 June 2014] Available from: doi:10.1056/NEJM199701093360207
  4. TAKATSUKI S, IVY DD. Current Challenges in Pediatric Pulmonary Hypertension Semin Respir Crit Care Med [online] 2013 Oct, 34(5):627-644 [viewed 20 June 2014] Available from: doi:10.1055/s-0033-1356461

Investigations - Screening/Staging

Fact Explanation
Genetic Screening [1] Mutations in the bone morphogenetic protein receptor II (BMPR2) gene have been identified in approximately 50% of patients with familial PAH (FPAH) and 25% of patients thought to have sporadic primary pulmonary hypertension. Also pulmonary hypertension has also been reported to occur in some individuals with Hereditary hemorrhagic telangiectasia (HHT). Defects of transforming growth factor-β receptor complex, including endoglin and activin receptor-like kinase 1 (ALK1) have been implicated in the autosomal dominant vascular dysplasia of HHT therefore genetic testing for these can be done [1]
Echocardiography [1] even though evaluation with electrocardiography for screening asymptomatic patients with Pulmonary hypertension can be done, since the incidence of disease is low not very effective. Staging of the disease is also possible with this [1]
Cardiopulmonary exercise tests [2] There is a correlation between the distance walked during a six-minute walk test and the severity of pulmonary hypertension, therefore can be used as a staging system [2]
References
  1. MCGOON MICHAEL. Screening, Early Detection, and Diagnosis of Pulmonary Arterial Hypertension . Chest [online] 2004 July [viewed 20 June 2014] Available from: doi:10.1378/chest.126.1_suppl.14S
  2. RUBIN LEWIS J.. Primary Pulmonary Hypertension. N Engl J Med [online] 1997 January, 336(2):111-117 [viewed 20 June 2014] Available from: doi:10.1056/NEJM199701093360207

Management - General Measures

Fact Explanation
Patient education [1] It's important to educate patients regarding the nature, course and prognosis of the disease and should be advised to avoid strenuous exercises, to avoid dehydration and excessive heat. Also they should be taught on medications, their side effects, and their interactions [1]
Dietary management [1] No specific diet is recommended but a low-sodium and low-fluid diet is preferred in patients with significant volume overload due to failure of right ventricle. [1]
Exercise [1] [4] They can perform mild symptom-limited aerobic activity and should avoid complete bed rest. Isometric exercises (weight lifting) are contraindicated. [1]
Treatment of heart failure [2] [3] [4] Diuretics are useful in reducing excessive preload in patients with right heart failure and also used as ancillary therapy [2]
Supplemental oxygen therapy [2] [4] Patients with hypoxemia may have symptomatic improvement with supplemental oxygen. [2]
Digoxin and other cardiac glycosides [2] [4] These are given in order to counteract the negative inotropic properties of the calcium-channel blockers. [2]
Anticoagulation [2] [4] Anticoagulation is recommended as therapy because there is an increased risk of thrombosis and thromboembolism due to sluggish pulmonary blood flow, dilation of the right heart chambers, venous stasis. Warfarin is the anticoagulant of choice, in doses adjusted to achieve an international normalized ratio of approximately 2.0. [2]
Pregnancy and birth control [4] pregnancy is associated with 30–50% mortality in patients with pulmonary hypertension therefore it is a contra-indication to pregnancy. Barrier contraceptive methods are thought to be safe [4]
References
  1. BENISTY J. I.. Pulmonary Hypertension. [online] 2002 December, 106(24):192e-194 [viewed 20 June 2014] Available from: doi:10.1161/​01.CIR.0000042762.47822.FE
  2. RUBIN LEWIS J.. Primary Pulmonary Hypertension. N Engl J Med [online] 1997 January, 336(2):111-117 [viewed 20 June 2014] Available from: doi:10.1056/NEJM199701093360207
  3. THOMAS K, SCHRöTTER H, HALANK M, ZIEMSSEN T. Fingolimod in a patient with heart failure on the background of pulmonary arterial hypertension and coronary artery disease BMC Neurol [online] :126 [viewed 20 June 2014] Available from: doi:10.1186/1471-2377-14-126
  4. GALIE N, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). European Heart Journal [online] December, 30(20):2493-2537 [viewed 20 June 2014] Available from: doi:10.1093/eurheartj/ehp297

Management - Specific Treatments

Fact Explanation
Pharmacological therapy with vasodilators [1] [2] [3] [4] [5] [6] [7] The rationale is based on the observation that vasoconstriction is a prominent feature of this disease. The most suitable vasodilators such as nitric oxide, epoprostenol (prostacyclin), and adenosine, Iloprost, Treprostinil, Beraprost are used [1] [2]
Pharmacological therapy with Endothelin receptor antagonists [2] [3] [4] [5] [6] [7] Since activation of the endothelin system has been demonstrated in these patients, these drugs such as Bosentan, Ambrisentan are used [2]
Pharmacological therapy with Phosphodiesterase type-5 inhibitors [3] [4] [5] [6] [7] Since inhibition of the cGMP-degrading enzyme phosphodiesterase type-5 results in vasodilatation through the NO/cGMP pathway at sites expressing this enzyme these drugs are used. Also pulmonary vasculature contains considerable amounts of phosphodiesterase type-5 [2] [3] [4] [5]
Pharmacological therapy with calcium channel blockers [2] [3] The following mechanisms contribute to the development of pulmonary hypertension. They are smooth muscle cell hypertrophy, hyperplasia, and vasoconstriction and this has led to the use of traditional vasodilators since the mid 1980s, principally involving the use of CCBs, but now not widely used [2] [3]
Surgical management with Transplantation and Septostomy [1], [3] Lung transplantation and combined heart–lung transplantation are performed for primary pulmonary hypertension as well as septostomy. Severely epressed right ventricular function can improve considerably with single- or double-lung transplantation and one-year survival rates after lung transplantation for primary pulmonary hypertension range from 65 to 70% [1]
References
  1. RUBIN LEWIS J.. Primary Pulmonary Hypertension. N Engl J Med [online] 1997 January, 336(2):111-117 [viewed 20 June 2014] Available from: doi:10.1056/NEJM199701093360207
  2. GALIE N, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). European Heart Journal [online] December, 30(20):2493-2537 [viewed 20 June 2014] Available from: doi:10.1093/eurheartj/ehp297
  3. TAKATSUKI S, IVY DD. Current Challenges in Pediatric Pulmonary Hypertension Semin Respir Crit Care Med [online] 2013 Oct, 34(5):627-644 [viewed 20 June 2014] Available from: doi:10.1055/s-0033-1356461
  4. KLINGS ES, VICHINSKY EP, MORRIS CR. Response to "Efficacy and safety of sildenafil for the treatment of severe pulmonary hypertension in patients with hemoglobinopathies: results from a long-term follow up " Haematologica 2014;99(2):e17-18. Haematologica [online] 2014 Feb, 99(2):e19 [viewed 20 June 2014] Available from: doi:10.3324/haematol.2013.099861
  5. YASEEN H, DARWICH M, HAMDY H. Is Sildenafil an Effective Therapy in the Management of Persistent Pulmonary Hypertension? J Clin Neonatol [online] 2012, 1(4):171-175 [viewed 20 June 2014] Available from: doi:10.4103/2249-4847.105958
  6. BECKER EM, STASCH JP, BECHEM M, KELDENICH J, KLIPP A, SCHAEFER K, ULBRICH HF, TRUEBEL H. Effects of Different Pulmonary Vasodilators on Arterial Saturation in a Model of Pulmonary Hypertension PLoS One [online] , 8(8):e73502 [viewed 20 June 2014] Available from: doi:10.1371/journal.pone.0073502
  7. SEFERIAN A., SIMONNEAU G.. Therapies for pulmonary arterial hypertension: where are we today, where do we go tomorrow?. European Respiratory Review [online] December, 22(129):217-226 [viewed 20 June 2014] Available from: doi:10.1183/09059180.00001713