Pulmonary Hypertension: a Deeper Look into WHO Group 1 and 4 Lana Melendres-Groves PH Program Director Pulmonary/Critical Care 1/27/16 Objectives Define pulmonary hypertension (PH), pulmonary arterial hypertension (PAH), and chronic thromboembolic pulmonary hypertension (CTEPH) Discuss the classification system of PH Describe the pathophysiology of PAH and CTEPH Detection and diagnosis of PH, PAH and CTEPH A little on management and medications for WHO grp 1 and 4 Suspicion of Pulmonary Hypertension Edema Shortness of breath Fatigue Dizziness/syncope Echo findings: Elevated PASP Right heart dilation Right heart dysfunction My attending told me so Presence of other disease processes PFT findings CT chest findings Presence of pulmonary embolism Definition of Pulmonary Hypertension (PH) PH refers to the presence of abnormally high pulmonary vascular pressure Normal mPAP: 8-20mmHg at rest PH: mPAP> 25mmHg at rest How is Pulmonary Arterial Hypertension (PAH) Defined? PAH is a syndrome resulting from restricted blood flow in the pulmonary arterial circulation resulting in increased pulmonary vascular resistance which causes right ventricular strain and ultimately failure Hemodynamic- mPAP >25mmHg definition of PAH:- PCWP 3 woods units Clinical Classification of Pulmonary Hypertension (Nice, 2013) 1.1 Idiopathic PAH (IPAH) 1.2 Heritable PAH 1.3 Drug- and toxin-induced PAH 1.4 Associated PAH Connective tissue disease HIV infection Portal hypertension Congenital heart disease Schistosomiasis 1. Pulmonary veno-occlusive disease (PVOD) and /or pulmonary capillary hemangiomatosis (PGH) 1. Persistent pulmonary hypertension of the newborn (PPHN) 2.1 LV systolic dysfunction 2.2 LV diastolic dysfunction 2.3 Valvular disease 2.4 Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies 3.1 COPD 3.2 Interstitial lung disease 3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern 3.4 Sleep-disordered breathing 3.5 Alveolar hypoventilation disorders 3.6 Chronic exposure to high altitude 5.1 Hematologic disorders 5.2 Systemic disorders 5.3 Metabolic disorders 5.4 Others 1. Pulmonary arterial hypertension (PAH) 2. PH due to left heart disease 3. PH due to lung disease and/or hypoxia 4. Chronic thromboembolic pulmonary hypertension (CTEPH) 5. PH with unclear multifactorial mechanisms Why do I care so much? And Why should you care so much? PH is a Rapidly Progressive, Ultimately Fatal Condition WHO Group 1 PAH WHO Group 2 Left-heart related WHO Group 3 Lung/hypoxia related WHO Group 4 CTEPH Based on a sample of 194 patients followed between 1981 and 1986, median survival was estimated at 2.8 years (IPAH) In a study of 379 patients referred to a single center between 1992 and 1998, patients with Group 2 PH had 7x higher mortality than left- sided heart failure alone 5-year survival rate in study of 84 total COPD patients was 36% in those with PH vs 62% in patients without PH In a study of 79 IPF patients, the 6.5- year mortality rate was 60% among those with PH vs 30% in patients with IPF alone Mean survival 6.8 years without surgical treatment in a study of 48 Japanese patients Pathogenesis of PAH: Aberrant Pathways Loss of Biological Balance in PAH Vasodilation Apoptosis Vasoconstriction Proliferation Vasodilation Apoptosis Vasoconstriction Proliferation SMC Endothelium elastic elasticlamina injury serum leak SMC PROLIFERATION & MIGRATION Pathobiology of PAH Prevalence of PAH Based of the French National Registry from 02-03 for PAH and IPAH: Consecutive adult patients 17 French specialty centers Prevalence of PAH: 15 cases/million Prevalence of IPAH: 5.9 cases/million Distribution of PAH Subtypes French Registry (n=674) IPAH 39.2% FPAH 3.9% CTD 15.3% CHD 11.3% Portal htn 10.4% Drugs and toxins 9.5% HIV 6.2% REVEAL (n=2525) IPAH 46.2% APAH 50.7% CTD/CVD 49.9% CHD 19.5% Drugs and toxins 10.5% Portal htn 10.6% Other 5.5% HIV 4.0% FPAH 2.7% Other 0.4% Prevalence of PAH in Connective Tissue Diseases Systemic lupus erythematosis (SLE): 0.5% to 17% Mixed Connective tissue disease (MCTD): up to 25% Systemic Sclerosis: 8% to 27% SLE MCTD Systemic Sclerosis Drugs and Toxins Associated with PAH Definite -Aminorex -Fenfluramine -Dexfenfluramine -Toxic rapeseed oil -Benfluorex -SSRIs Likely -Amphetamines -L-tryptophan -Methamphetamines -Dasatinib Possible -Cocaine -Phenylpropanolamine -St. Johns Wort -Chemotherapeutic agents -Interferon alpha and beta -Amphetamine-like drugs Unlikely -Oral contraceptives -Estrogen -Cigarette smoking Portal Hypertension Prevalence of PAH in portal htn ranges from 2% to 6% Risk of developing PAH increases with duration of portal hypertension Liver disease is most common cause of portal hypertension, but it can be secondary to nonhepatic causes Switching WHO Groups On to Group 4: CTEPH What is CTEPH? Vascular disorder characterized by: Organized thrombotic obstruction in the pulmonary arteries May involve small-vessel vasculopathy that is indistinguishable from idiopathic PAH Defined by the following observations after 3 months of effective anticoagulation: - mPAP >25mmHg - PCWP