Snapshot A 37-year-old woman is referred to the pulmonologist’s office from her PCP for worsening shortness of breath. She reports that she has had increasing dyspnea on exertion and fatigue for the past 3 years, but it has gotten much worse in the last 2 months. She used to walk around the neighborhood with her friends but now gets short of breath with occasional chest pain just walking around the house. Her past medical history is otherwise completely negative. On physical exam, she has a JVP of 13 cm H2O, a loud P2, an S3, a right-sided heave, a liver palpable 3 cm below the costal margin, and bilateral leg edema. She is sent for a trans-thoracic echocardiogram which estimates a high pulmonary artery systolic pressure and shows right ventricular hypertrophy and right heart failure. The diagnosis is confirmed with a right heart catheterization and she is started on epoprostenol. Introduction Clinical definition mean pulmonary artery pressure ≥ 20 mmHg normal = 8-20 mmHg gold standard for measurement is right heart catheterization Epidemiology incidence varies by etiology; affects all ages, races, and genders can be very rare (~4 cases per million for idiopathicpulmonary hypertension (IPAH)) or relatively common 10-40% of patients with at-risk associated diseases (below) demographics females > males up to 9:1 (for IPAH) Primary Etiologies of Pulmonary Hypertension Etiology Key Points Idiopathic pulmonary arterial hypertension (IPAH) By definition, the cause is unknown Hereditary pulmonary arterial hypertension (HPAH) Mutation in the BMPR-2 gene acts normally to inhibit smooth muscle growth Mnemonic: Blocker of Muscle PRoliferation More common in women (9:1) Poor prognosis Secondary Etiologies of Pulmonary Hypertension Etiology (secondary to) Key Points Autoimmune disease Systemic sclerosis > SLE >> RA Inflammation of vessel wall leads to scarring and stiff vessels Drugs Direct pulmonary vasoconstriction e.g., cocaine or methamphetamine Infection Schistosomiasis leading cause of pulmonary hypertension in endemic areas HIV Left-to-right shunt Increased flow to pulmonary system e.g., from congenital heart defects Left heart disease Decreased cardiac output backs blood into pulmonary circuit e.g., left heart failure or mitral valvular disease Lung disease/hypoxia Decreased oxygen delivery leads to hypoxemic pulmonary vasoconstriction e.g., COPD, obstructive sleep apnea, obesity hypoventilation syndrome, or high altitudes Thromboembolic disease Chronic, recurrent micro-emboli decrease the cross-sectional area of pulmonary vessels Unclear/miscellaneous e.g., carcinoid syndrome, sarcoidosis, vasculitis, or metabolic disorders Pathogenesis common final pathway for all etiologies luminal injury from increased pulmonary pressure smooth muscle proliferation of the media and intima fibrosis resulting in plexiform lesions on pathology fibrosis leads to stiff vessels increased pulmonary vascular resistance (PVR) right ventricle has to pump harder to overcome resistance right ventricular hypertrophy right heart failure Associated conditions schistosomiasis systemic sclerosis SLE HIV persistent pulmonary hypertension of the newborn Prognosis progressive and fatal if untreated incurable treatment focuses on slowing the disease progression rate of progression is variable for IPAH and HPAH, 5-year survival is approximately 50% Presentation Symptoms dyspnea on exertion fatigue if subsequent right heart failure exertional chest pain (angina) exertional syncope swelling RUQ pain (from hepatic congestion) anorexia (from hepatic congestion) Physical examination loud P2 on auscultation right-sided heave from right ventricular hypertrophy if subsequent right heart failure elevated JVP hepatomegaly S3 heart sound Imaging Echocardiogram usually first step in the workup right ventricular hypertrophy enlarged pulmonary arteries estimated pulmonary arterial systolic pressure estimated from flow rate across the tricuspid valve Chest radiograph enlarged pulmonary arteries pruning of peripheral vessels CT angiography enlarged pulmonary trunk and pulmonary arteries Studies Labs BNP non-specific Diagnostic procedures right heart catheterization allows measurement of pulmonary arterial pressures gold standard for diagnosis Diagnosis clinical diagnosis by appropriate history, physical exam, and imaging/lab findings very likely if echocardiogram estimates high pressures if few or ambiguous clinical findings, may need to confirm with right heart cath (early IPAH and HPAH) Differential Congestive heart failure (without PH) clinically very similar distinguishing factors typically, a long history of heart attacks, coronary artery disease, hypertension, and/or other risk factors for heart failure can be distinguished by echo and/or cath Coronary artery disease can also present with exertional chest pain, shortness of breath, and fatigue distinguishing factors positive stress testing coronary vessel occlusion and normal pulmonary pressures upon catheterization Liver disease can present with lower extremity swelling and RUQ pain distinguishing factors lack of respiratory symptoms normal JVP Treatment Management approach as PH is incurable, management is focused on slowing disease progression and alleviating symptoms for PH secondary to other disease (heart, lung, etc…), treat the underlying cause Medical for symptoms oxygen diuretics exercise therapy PH-specific therapies prostacyclin (PGI2) epoprostenol (IV) and iloprost (inhaled) mechanism vasodilation side effects jaw pain and flushing endothelin receptor antagonists (bosentan) endothelin-1 (ET-1) is a potent vasoconstrictor in the lungs mechanism blocks the ET-1 receptor to decrease vasoconstriction side effects hepatotoxic PDE-5 inhibitors (sildenafil) nitric oxide is a vasodilator PDE-5 helps to break down nitric oxide mechanism blocks PDE-5, increasing NO, and thus vasodilation side effects headache Complications Cor pulmonale right-sided congestive heart failure secondary to pulmonary disease Chronic hypoxemic respiratory failure