2) Maacy Traning Module-PAH Epidemiology,Prevalence & Pathophysiology.pptx

PAH Medical Training What is Asthma Section Objective You need to know from this section • What is PAH? • What is the PAH component. • PAH effect and Burden • PAH prevalence global. • PAH prevalence in KSA PH Definition and its types Pulmonary Hypertension • Pulmonary hypertension is a type...

PAH Medical Training What is Asthma Section Objective You need to know from this section • What is PAH? • What is the PAH component. • PAH effect and Burden • PAH prevalence global. • PAH prevalence in KSA PH Definition and its types Pulmonary Hypertension • Pulmonary hypertension is a type of high blood pressure that affects the arteries in the lungs and the right side of the heart. In one form of pulmonary hypertension, called pulmonary arterial hypertension (PAH), blood vessels in the lungs are narrowed, blocked or destroyed. • The damage slows blood flow through the lungs. • Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure ≥25 mm Hg at rest, measured during right heart catheterization. • The heart must work harder to pump blood through the lungs. The extra effort eventually causes the heart muscle to become weak and fail. • In some people, pulmonary hypertension slowly gets worse and can be life-threatening. There's no cure for pulmonary hypertension. But treatments are available to help you feel better, live longer and improve your quality of life. Pulmonary Hypertension Types PH classification and Groups: • Not all pulmonary hypertension (PH) is the same. PH is a general term used to describe high blood pressure in the lungs from any cause. There are five different groups of PH based on different causes. These groups are defined by the World Health Organization (WHO) and are referred to as PH WHO Groups. Group 1 3% Pulmonary Arterial Hypertension (PAH) • WHO Group 1 refers to pulmonary arterial hypertension (PAH), which is caused when the arteries in the lungs become narrowed, thickened or stiff. Group 2 68% Pulmonary Hypertension Due to Left Heart Disease • WHO Group 2 includes PH due to left heart disease. • In this group of PH, the arteries and lungs are not as thick or stiff as WHO Group 1, but there are problems with how the heart squeezes or relaxes, or problems with the valves on the left side of the heart. • Because of this, the left heart is unable to keep up with the blood returning from the lungs — causing a “backup” of blood which raises pressure in the lungs. • WHO Group 2 is the most common form of PH. Group 3 9% Pulmonary Hypertension Due to Lung Disease • WHO Group 3 includes PH due to chronic lung disease and/or hypoxia (low oxygen levels). • These lung diseases include obstructive lung disease where the lung airways narrow and make it harder to exhale (e.g. COPD or emphysema); restrictive lung disease in which the lungs have a tough time expanding when one inhales (e.g. interstitial lung disease or pulmonary fibrosis); sleep apnea; and living in an area of high altitude for a long period of time. • Arteries in the lungs tighten so that blood can only go to areas of the lungs that are receiving the most air and Group 4 2% Pulmonary Hypertension Due to Chronic Blood Clots in the Lungs. • WHO Group 4 is called chronic thromboembolic pulmonary hypertension (CTEPH). • CTEPH can occur when the body is not able to dissolve a blood clot in the lungs. • This can lead to scar tissue in the blood vessels of the lungs, which blocks normal blood flow and makes the right side of the heart work harder. • This type of PH is unique because it can potentially be cured through pulmonary thromboendarterectomy (PTE) surgery to remove the blood clots. • However, not all CTEPH patients are eligible for this surgery. • A drug is also available for CTEPH patients if a doctor determines that a patient is not Group 5 15% Pulmonary Hypertension Due to Unknown Causes. • WHO Group 5 is where PH is secondary to other diseases in ways that are not well understood. • These associated conditions include, but are not limited to, sarcoidosis, sickle cell anemia, chronic hemolytic anemia, splenectomy (spleen removal) and certain metabolic disorders. Pulmonary Hypertension Types Group 1 Pulmonary Arterial Hypertension (PAH): • The right side of the heart must work harder to push blood through these narrowed arteries. • This extra stress can cause the heart to lose its ability to pump enough blood through the lungs to meet the needs of the rest of the body. • There are several types of PAH. Idiopathic PAH (IPAH) is PAH that occurs without a clear cause. • Heritable PAH (HPAH) is linked to genes that are inherited from family members. • PAH can also develop in association with other medical conditions including congenital heart disease, liver disease, HIV and connective tissue diseases — such as scleroderma and lupus. • PAH can even be associated with past or present drug use, such as the use of methamphetamine or certain diet pills. • While there are management options for PAH, there is no known cure. Pulmonary Hypertension (Types % of incidence) If left untreated, PH can lead to: • Right heart failure and death. Fortunately, because of major advancements made in the past two decades, therapies that target the pulmonary arteries (PH-targeted therapies) are available to help relieve symptoms, improve quality of life and slow down the progression of the disease in patients with WHO Group 1. • Patients with WHO Groups 2 and 3 can benefit from treating the underlying left heart and lung diseases, respectively. Patients with WHO Group 4 can benefit from either a surgery to remove the clots or a PHtargeted therapy if they are unable to have the surgery or have PH remaining after the surgery. Pulmonary Arterial Hypertension(Group 1) Healthy Pulmonary Artery Arteries are healthy and flexible, blood flows easily through the vessels. Mild PAH Thick and stiff artery walls limit blood flow and increase the resistance. Moderate PAH Blood flow is restricted as the artery narrows. Pulmonary Hypertension Due to Left Heart Disease(Group 2) Systolic Dysfunction Diastolic Dysfunction Severe PAH with Plexiform Lesions Advanced vascular lesions (abnormal growth) and thrombi (blood clots) form. Pulmonary Hypertension Due to Lung Disease (Group 3) Pulmonary Hypertension Due to Chronic Blood Clots in the Lungs (Group 4) PAH Epidemiology / Pathology PAH Epidemiology / Pathology PAH is uncommon relative to other forms of PH, with an estimated prevalence of 15 to 50 per million Globally. • Group 1 PAH conditions are characterized by: • • • • Common causes of PAH include: • • • • • • Pulmonary artery vascular cell proliferation. Luminal narrowing. Loss of cross-sectional area. Idiopathic Heritable Drug-induced Connective tissue disease Congenital heart disease–associated. Rarer causes of PAH include: • • • HIV Schistosomiasis Portal hypertension. • Randomized trials have shown effectiveness of vasodilator agents, including phosphodiesterase-5 inhibitors, endothelin receptor antagonists, soluble guanylate cyclase inhibitors, and prostacyclin analogues in group 1 PAH. • Hemodynamically, PAH is characterized by precapillary PH with mPAP >20 mm Hg, an end-expiratory pulmonary artery wedge pressure PAWP <15 mm Hg and a pulmonary vascular resistance (PVR) >3 Wood Units. PAH Epidemiology / Pathology • PAH incidence 6 in USA and Europe. • Prevalence 48–55 cases/million adults in USA and Europe. • IPAH was the most common subtype (50–60% of all cases). • The incidence and prevalence of PH in Saudi Arabia is unknown (estimated number of cases is from 750 to 800) • Affects 4 times more as many females as males. • Historically, idiopathic PAH was predominantly recognized in younger females (30 to 35 years old) • However, there is increasing prevalence of PAH affecting more elderly patients with a more balanced sex ratio, comorbidities, and potentially less favorable response to therapy. PAH Epidemiology / Pathology PAH Epidemiology / Pathology PAH Epidemiology / Pathology PAH Epidemiology / Pathology • Exact cause of PAH remains unknown • Endothelial dysfunction occurs early on in the disease process • Endothelial dysfunction results in: • • • • Reduced production of vasodilators Over production of vasoconstrictors Endothelial and smooth muscle cell proliferation Remodeling of the pulmonary vascular bed and increased pulmonary vascular resistance (PVR ) • Increase in pulmonary vascular resistance (PVR): • • Leads to right ventricular overload Leads to right ventricular failure and premature death • Three pathways are involved: • • • Prostacyclin (prostaglandin) Nitric oxide (NO)− Cyclic guanosine monophosphate (GMP)- phosphodiesterase 5 Endothelin • Platelets likely play an important role as pro-coagulants by increasing the platelet release of serotonin, vascular endothelial growth factor, and platelet-derived growth factor. PAH Epidemiology / Pathology •Reduced production of vasodilators • Prostacyclin • Potent vasodilator • Potent inhibitor of platelet activation • Therapy with synthetic forms of prostacyclin may help to correct this deficiency • Nitric oxide • • • • Potent vasodilator Possesses anti-proliferative properties Vasodilatory effect is mediated by cGMP Rapidly degraded by phosphodiesterase •Increased production of vasoactive compounds • Endothelin (ET) • Elevated levels are seen in PAH patients • Levels correlate with disease severity • Deleterious effects mediated through ETA and ETB receptors • • • • Fibrosis Hypertrophy and cell proliferation Inflammation Vasoconstriction • Endothelin receptor antagonists can block these effects •ET, nitric oxide and Prostacyclin have been the principal focus of research into treatments for PAH Thank You