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Similar a Pulmonary Arterial Hypertension (PAH) presentation
Similar a Pulmonary Arterial Hypertension (PAH) presentation (20)
Pulmonary Arterial Hypertension (PAH) presentation
- 1. Pulmonary Arterial Hypertension (PAH) By: Yury Viknevich
- 2. Overview Definition Types Etiology Background: Pathophysiology Risk factors Symptoms Diagnosis Classification Complications Treatment News
- 3. Definition Normal pulmonary artery pressure is 8-20 mm Hg at rest Pulmonary hypertension is pressure in the pulmonary artery that is greater than 25 mm Hg at rest or 30 mmHg during physical activity
- 4. Types Group 1 PAH (pulmonary arterial hypertension) Group 2 PH (left heart disease) Group 3 PH (lung disease) Group 4 PH (thromboembolic disease) Group 5 PH (multifactorial)
- 5. Etiology Estimated prevalence of 15-50 cases per million Approximately 10% of patients diagnosed with pulmonary arterial hypertension (PAH) have a family history of the disease ◦ Referred to as having familial PAH (FPAH) Idiopathic PAH (IPAH) has an annual incidence of 1-2 cases per million people in the US and Europe Higher incidence in women
- 6. Background: Pathophysiology Life-threatening condition that gets worse over time ◦ It is high blood pressure (BP) in the arteries that go from the heart to the lungs Can be genetic or caused by another condition
- 7. Background: Pathophysiology Platelets, fibroblasts, and circulating cells are involved in the progression of PAH The phenotypical change of pulmonary arterial smooth muscle cells (PASMCs) and pulmonary arterial endothelial cells (PAECs) results from multiple genetic and acquired defects and is probably the major cause for the onset of the disease ◦ Increased PASMC contraction, increased PASMC proliferation and inhibited PASMC apoptosis, monoclonal PAEC proliferation, and endothelial injury all are involved in the development of sustained pulmonary vasoconstriction, lumen obliteration of small pulmonary arteries with plexiform lesions, and pulmonary vascular wall thickening due to medial hypertrophy
- 8. Risk factors Congestive heart failure Blood clots in the lungs Family history Lupus Scleroderma Emphysema Chronic bronchitis Pulmonary fibrosis Sleep apnea Cirrhosis HIV/AIDs Sex (young female) Drug induced
- 9. Risk factors: Drug induced Definite Possible Aminorex Cocaine Fenfluramine Phenylpropanolamine Dexfenfluramine St John's Wort Toxic rapeseed oil Chemotherapeutic agents Benfluorex Selective serotonin reuptake inhibitors Dasatinib Pergolide Likely Unlikely Amphetamines Oral contraceptives L-Tryptophan Oestrogen Methamphetamines Cigarette smoking
- 10. Symptoms Shortness of breath (SOB) ◦ Usually, starts slowly and gets worse over time Chest pain (CP) Fatigue or dizziness (syncope) Passing out Swelling in the ankles and legs (edema) Racing pulse or heart palpitations
- 11. Diagnosis Hard to spot/diagnose because it mimics those of other similar conditions ◦ Will assess medical history and use one or more tests (ie. blood test, chest X-ray, CT scan, MRI, electrocardiogram, echocardiogram, heart catheterization, pulmonary function test, lung biopsy)
- 14. Classification Class I. Diagnosed with pulmonary hypertension, you have no symptoms with normal activity Class II. Have symptoms at rest, but you experience symptoms such as fatigue, shortness of breath or chest pain with normal activity Class III. Comfortable at rest, but have symptoms when active Class IV. Symptoms with physical activity and while at rest
- 15. Complications Right-sided heart enlargement and heart failure Blood clots Arrhythmia Bleeding
- 17. Treatment overview Figure Legend: Evidence-Based Treatment Algorithm APAH = associated pulmonary arterial hypertension; BAS = balloon atrial septostomy; CCB = calcium channel blockers; ERA = endothelin receptor antagonist; sGCS = soluble guanylate cyclase stimulators; IPAH = idiopathic pulmonary arterial hypertension; i.v. = intravenous; PDE-5i = phosphodiesterase type-5 inhibitor; s.c. = subcutaneous; WHO-FC = World Health Organization functional class.
- 18. Treatment: Non-pharmacologic Salt and volume management Supervised exercise (not too strenuous) Avoiding pregnancy ◦ The mortality rate approaches 30 percent Immunization ◦ Specifically, influenza and pneumococcal Improving diet Psycho-social support
- 19. Treatment: Pharmacologic All: anticoagulants ± diuretics ± digoxin ± oxygen ◦ Long-term oxygen therapy is suggested to maintain arterial blood O2 pressure at 60 mmHg
- 20. Treatment: Pharmacologic Acute vasoreactive testing (IPAH or APAH, ONLY) ◦ Positive: use high dose oral CCB (ie. nifedipine, diltiazem, or amlodipine) use long term ◦ Negative: depends on risk Low/High risk: endothelin receptor antagonist (ERA) or Phosphodiesterase Type 5 (PDE5) Inhibitors (oral), [prostanoids: epoprostenol (IV) or treprostinil (IV/SC), Iloprost (inhaled)], soluble guanylate cyclase (sGC) stimulators
- 21. Treatment: Pharmacologic Low or intermediate risk: monotherapy or oral combination therapy High risk: combination therapy including IV prostacyclin analogs
- 22. Treatment: Pharmacologic Prostanoids: ◦ Epoprostenol (Flolan, Veletri): 2 ng/kg/min IV infusion every 15 min (initial) MOST COMMON ◦ Treprostinil (Remodulin, Tyvasco): Remodulin (IV) = 1.25 ng/kg/min continuous SQ or central line IV infusion (initial) Tyvasco: QID inhalation ◦ Iloprost (Ventavis): 2.5 -5 mcg/inhalation 6- 9x/day Class AE: D/N/V (dose limiting), flushing, hypotension, anxiety, chest pain, tachycardia, edema ◦ Chronic use: anxiety, flu-like symptoms, and jaw pain (lockjaw with Iloprost)
- 23. Treatment: Pharmacologic ERAs: ◦ Bosentan (Tracleer): 62.5 mg PO bid x 4 wks and then 125 mg bid BBW: hepatotoxicity and Cat X CI:cyclosporin and glyburide AE: HA, decrease Hgb, anemia, increase LFTs, upper respiratory tract infections, edema, male infertility Monitor: LFTs ◦ Ambrisentan (Letairis): 5 or 10 mg PO qd BBW: Cat X AE: peripheral edema, HA, decrease Hgb, flushing, palpitations, congestion Monitor: Hgb and hematocrit Macitatan (Opsiumit): 10 mg PO qd ◦ BBW: hepatotoxicity and Cat X ◦ CI: strong inducers of 3A4 ◦ AE: anemia, cold-like symptoms, bronchitis, HA, flu and UTI ◦ Monitor: LFTs
- 24. Treatment: Pharmacologic PDE-5 Is: ◦ Sildenafil (Revatio): 10 mg IV tid OR 20 mg PO tid (4-6 hr apart) ◦ Tadalafil (Adcirca): 40 mg PO qd OR 20 mg PO qd with mild – moderate renal/hepatic impairment (avoid with CrCl < 30 mL/min) Class ◦ CI: nitrates or sildenafil with PI based regimen, severe hepatic impairment ◦ AE: dizzy, sudden drop in BP, HA, flush, dyspepsia, back pain (Adcirca), and epistaxis
- 25. Treatment: Pharmacologic sGC stimulant: ◦ Riociguat (Adempas): 1 mg PO TID (initial) Antacids decrease absorption and should not be taken within 1 hr of taking medication BBW: Cat X (do not become pregnant during and 1 month after treatment) CI: nitrates or NO donors, PDE inhibitors AE: HA, dyspepsia and gastritis, dizziness, N/D/V, hypotension Monitor: BP (baseline and every 2 weeks)
- 26. Treatment: Pharmacologic If fail therapy, add another agent If fail that, lung transplant or atrial septostomy (Last option)
- 27. News FDA approved Uptravi (selexipag) tablets to treat adults with pulmonary arterial hypertension (PAH): approved through the Orphan drug designation ◦ Developed by Actelion Selexipag is a selective prostacyclin- receptor agonist that targets a well- known disease pathway that opens blood vessels to the lungs and improves heart function
- 28. Thank you November is pulmonary hypertension month !!!!
- 29. Questions
- 30. References http://www.healthline.com/health/pulmonary-hypertension/how-pah- diagnosed#Tests5 http://www.webmd.com/lung/pulmonary-arterial-hypertension#1-4 https://dcri.org/events/presentations/pulmonary-hypertension-2014/Fortin- Non%20Pharmacologic.pdf http://content.onlinejacc.org/article.aspx?articleid=1790601 http://circ.ahajournals.org/content/111/5/534 http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm478599.ht m http://familydoctor.org/familydoctor/en/diseases-conditions/pulmonary- hypertension/causes-risk-factors.html http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/docs/fs_pulmonary_hyperte nsion.pdf http://www.pah-info.com/How_common_is_PAH http://www.mayoclinic.org/diseases-conditions/pulmonary- hypertension/symptoms-causes/dxc-20197481 http://reference.medscape.com/drug/adempas-riociguat-999863#4 http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/pulmonary- arterial-hypertension/risks-symptoms-pul-arterial-hypertension.html
Notas del editor
- For times sake, will talk only about PAH.
- Due to the non-specific nature of the symptoms, PAH is unfortunately most frequently diagnosed when patients have reached an advanced stage of disease IPAH: rare progressive disease characterized by abnormally high blood pressure (hypertension) in the pulmonary artery. Persistent pulmonary hypertension of the newborn (PPHN) arises when the normal decrease in pulmonary vascular tone does not occur after birth. Severe PPHN has been estimated to occur in 0.2% of live-born term infants, and some degree of pulmonary hypertension complicates the course of more than 10% of all neonates with respiratory failure
- With PAH, the tiny arteries in your lungs become narrow or blocked. Therefore, it is harder for blood to flow through them, and that raises the blood pressure in the lungs. The heart has to work harder to pump blood through those arteries, and after a while the heart muscle gets weak. Eventually, it can lead to heart failure. Can cause PAH: Congestive heart failure Blood clots in the lungs HIV Illegal drug use (like cocaine or methamphetamine) Liver disease (such as cirrhosis of the liver) Lupus, scleroderma, rheumatoid arthritis, and other autoimmune diseases A heart defect you're born with Lung diseases like emphysema, chronic bronchitis, or pulmonary fibrosis Sleep apnea
- Accordingly, future efforts directed at developing effective therapeutic strategies for PAH should target multiple genes, gene products, and signal transduction pathways. Plexiform lesions are a characteristic vascular change of pulmonary arteries “medial hypertrophy” or enlargement of the muscular layer of the pulmonary artery
- Anorexigen-associated PAH: Appetite suppressant drugs were the first well-established risk factors for the development of PAH fenfluramine-induced PAH patients: share clinical, functional, haemodynamic and genetic features with idiopathic PAH patients, as well as similar overall survival rates. These observations suggest that fenfluramine derivatives may act as a trigger for PAH without influencing its clinical course. Benfluorex is a benzoate ester that shares similar structural and pharmacological characteristics with fenfluramine derivatives. The active and common metabolite of each of these molecules is norfenfluramine, which itself has a chemical structure similar to that of amphetamines. Given, that benfluorex shares the same active metabolite as fenluramine derivatives, it is highly probable that benfluorex triggers PAH. Amphetamines, methamphetamines and cocaine are considered to be risk factors for PAH, based on case reports and pharmacological similarities to fenfluramine. Dasatinib-induced PAH: a large inhibition spectrum and lack of specificity of TKIs may be responsible for unexpected toxicities, even at the pulmonary vascular level.
- RF: heard disease, congenital heart defects, scleroderma (chronic connective tissue disease generally classified as one of the autoimmune rheumatic diseases), HIV, a family history of PAH
- Example
- Right heart catheterisation (RHC) plays a central role in identifying pulmonary hypertension (PH) disorders, and is required to definitively diagnose pulmonary arterial hypertension (PAH) gold standard for diagnosis. Characterised by the presence of pre-capillary PH, PAH is determined by a PAWP ≤15 mmHg in addition to a mean PAP ≥25 mmHg at rest and a pulmonary vascular resistance (PVR) >3 Wood units
- LIFE LONG THERAPY!!!
- Chronic treatment: after diagnosis Anticoagulant: prevent clot formation (ex. Warfarin) Digoxin: allows heart to beat forcefully Diuretics: reduce fluid (ex. Lasix 40 mg bid-usual)
- This is the next test that is done to determine what medication to add to the patients drug regimen. This is only for patients with idiopathic, heritable or drug-induced PAH can undergo an acute vasoreactor test if necessary. Also, this test is used for initial treatment, if not already on therapy. Acute vasoreactive testing: identify the small minority of patients who may benefit from an oral calcium channel blocker. Inhaled nitric oxide (iNO) is the compound of choice for the acute test and intravenous epoprostenol or adenosine may also be used as an alternative (but with a risk of systemic vasodilator effects). More recently, inhaled iloprost has been able to identify patients who may benefit from long-term therapy with CCBs. Therapy will be chronic!!
- Monotherapies with the strongest evidence include endothelin receptor antagonists and phosphodiesterase type 5 inhibitors, while the combination therapy with the strongest evidence is ambrisentan plus tadalafil
- Prostanoids: potent vasodilators (pulmonary and systemic vascular beds) + inhibit platelet aggregation. Avoid interruption in therapy and IV is most potent. May incr effects of antihypertensive and antiplatelets. Epoprostenol: Alter the infusion by 1- to 2-ng/kg/min increments at intervals sufficient to allow assessment of clinical response. Given through a central catheter.
- ERAs: vasoconstrictor with cellular proliferative effects. Bosentan and Ambrisentan REMS program Don’t use with St. John’s wort or grapefruit juice Bosentan level may incr with 2c8/9 and 3a4 inh
- PDE-5 Is: incr cGMP concentrations lead to pulmonary vasculature relaxation and vasodilation. Sudden vision loss or vision problems, hearing problem or hearing loss (rare) Caution with the use of alpha blockers at the same time
- Riociguat does so via a dual mechanism of action: It sensitizes sGC to endogenous NO, and it directly stimulates sGC receptors independent of NO availability, resulting in vasorelaxation and antiproliferative effects. Approved 2013. REMS program
- Atrial septostomy is a procedure where a small hole is made in the wall between the left and right atria of the heart. The hole can be made using a cardiac catheter (a thin flexible tube, which is inserted into the chambers or blood vessels of the heart).
- Common side effects observed in those treated with Uptravi in the trial include headache, diarrhea, jaw pain, nausea, muscle pain (myalgia), vomiting, pain in an extremity, and flushing.