© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View menu, select the Slide Show option * To help you as you prepare a talk, we have included the relevant text from ITC in the notes pages of each slide

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. in the clinic Pulmonary Hypertension

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. What is pulmonary hypertension and what causes it?  Pulmonary hypertension (PH)  Mean pulmonary arterial pressure (PAP): >25 mm Hg  Elevated PAP burdens normally thin-walled right ventricle  Without treatment, right heart dysfunction = progressive symptoms, often eventually death  PH classified into 5 categories, each with a different…  Mechanism for the elevated PAP  Natural history  Approach to treatment

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. What causes pulmonary hypertension?  PH due to left heart disease (most common cause)  Systolic or diastolic left heart dysfunction  Mitral or aortic valve disorders  PH due to chronic hypoxemic lung disease  Obstructive lung disorders; interstitial lung disease  Sleep-disordered breathing  PH due to embolic disease  Miscellaneous causes  Pulmonary arterial hypertension (PAH)  Heritable / genetic abnormalities; idiopathic  Risk factors: collagen vascular diseases, HIV infection, liver disease, anorectic agent use

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. Who should be screened? Patients with…  Systemic sclerosis  Family history of a heritable form of PAH  Portal hypertension considered for organ transplant  Increased perioperative mortality with elevated mean PAP  Therapy may be needed prior to transplantation  Annual screening recommended in this setting

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. What are the symptoms?  Progressive dyspnea (most common symptom)  Fatigue  Chest pain  Presyncope / syncope  Lower extremity edema  Palpitations  Hoarseness from Ortner syndrome (rare)

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. What are the physical exam findings?  Accentuated intensity of pulmonary second heart sound  Tricuspid regurgitant murmur  Pulmonary insufficiency murmur  Right ventricular S3 or S4  Parasternal heave or subxiphoid thrust  Jugular venous distension  Peripheral edema  Hepatomegaly  Ascites

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. What is the role of echocardiography patients with suspected PH?  One of best tests to evaluate for possible PH  May report an estimate of systolic PAP  May provide information on cause of PH and symptoms  ECHO evaluating dyspnea or cardiac murmur may find PH  Indicators of more severe disease  Right atrial or ventricular enlargement  Hypertrophy; decreased right ventricular function  Severe elevations in right ventricular pressure may cause leftward deviation of interventricular septalum  Pericardial effusion

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. What other tests should be ordered in the evaluation of PH?  Autoantibody testing for collagen vascular disease  Brain natriuretic peptide or N-terminal BNP  Chest radiography; ECHO; EKG  CBC; electrolytes / creatinine measurement  HIV serologic testing  Liver function testing  Pulmonary function testing  Oxyhemoglobin saturation at rest and with exertion  Polysomnography  Radionuclide ventilation-perfusion imaging  Right heart catheterization  Six-minute walking distance

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. Which patients require cardiac catheterization?  Right heart catheterization  Required if PAH suspected (before advanced medical Rx)  Also helps identify unrecognized left heart dysfunction and pulmonary venous hypertension  Left heart catheterization  Often done concurrently, particularly if risk for CAD  No right heart catheterization needed…  PH known to be due to left heart or chronic pulmonary disease AND and cath not needed to guide management  Presence of PH itself doesn’t usually alter therapy

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. How should right heart catheterization be done when PH is a consideration?  Assess for possible left-to-right shunts  Measure oxygen saturation in central veins, right atrium, right ventricle, pulmonary artery  Increased oxyhemoglobin saturation suggests oxygenated blood being shunted to right-sided circulation  Measure hemodynamics accurately  At end of exhalation + level equipment at mid-thoracic line  Unsure of wedge?  Measure left ventricular end-diastolic pressure simultaneously  Test pulmonary vasoreactivity in PAH

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. What are the requirements for the diagnosis of PAH?  Presence of PH  Mean PAP > 25 mm Hg  Absence of pulmonary venous hypertension  Left atrial or “wedge” pressure < 15 mm Hg  Elevated pulmonary vascular resistance  > 3 Wood units  Exclusion of significant chronic hypoxemic lung disease  Exclusion of chronic thromboembolic disease

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. When should a clinician consider consultation with a specialist in diagnosing pulmonary hypertension?  Uncertainty regarding the diagnosis  Multiple comorbid conditions that may complicate diagnosis or treatment  High-risk features or NYHA functional class III or IV  Refer to a specialized center for evaluation

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. CLINICAL BOTTOM LINE: Diagnosis and Screening…  Confirm elevated pulmonary pressures  Evaluate for potential causes  ECHO; chest X-ray  Ventilation-perfusion scanning  Pulmonary function and blood testing  Assess disease severity  Measure oxyhemoglobin saturation  6-minute walking distance  Blood BNP  Right heart catheterization  Mandatory if therapy directed at PH itself (e.g., PAH)

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. What is the approach to treatment of PH?  Identify the cause  Chronic cardiac or pulmonary disease  Treat the underlying condition  Oxygen therapy  Maintain oxygen saturation ≥90%  Right heart dysfunction  Minimize fluid overload and dyspnea  Use diuretics  Restrict salt  Monitor weight

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. How should patients with PH due to left heart disease be treated?  Systolic HF  Use: ACE inhibitors; β-blockers; diuretics  Possibly: cardiac resynchronization, implantable cardioverter defibrillator placement, digitalis  HFpEF  Control BP + heart rate with β-blockers, diuretics  Left HFrEF  Differentiate from PAH  Don’t use prostacyclin analogues, endothelin antagonists  PH secondary to left valvular heart disease  Evaluation for correction of valvular disease

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. How should patients with PH due to lung disease be treated?  Optimize treatment of underlying cause  Sleep apnea (minimize nocturnal desaturation)  COPD  Idiopathic lung disease  Use supplemental oxygen to avoid hypoxia  Enroll in pulmonary rehabilitation  Don’t use PAH therapy in PH due to lung disease

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. How should patients with chronic thromboembolic PH be treated?  Prevention of recurrent clot / embolism (anticoagulation)  Pulmonary thromboendarterectomy (PTE)  Refer to center experienced in procedure and postop  Improves symptoms in most patients  Surgical mortality at experienced centers: <5%  Use medical therapy directed at PH only when…  PTE impossible due to distal location of disease within pulmonary vasculature  Therapeutic bridge needed until PTE performed  Patient decides not to have PTE

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. What drugs are available for the treatment of PAH?  Diuretics  Supplemental oxygen  Calcium-channel blockers (trial only if demonstrated vasoreactivity)  Anticoagulants  Digoxin Advanced therapies  Endothelin Antagonists (for lower risk patients)  Phosphodiesterase-5 Inhibitors (for lower risk patients)  Prostacyclins (for higher risk patients)

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. Is there a role for combination therapy in PAH?  Sequential addition of advanced therapies: current model  Initial therapy: based on illness severity + functional class  If PAH worsens: add therapies until treatment goals met  Approach shown to improve 6-min walking distance and delay clinical worsening  Combination therapy  Optimum and safest approaches not yet established  Investigations ongoing

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. What is the role of lung transplantation?  Treats underlying pulmonary condition in patients with…  Late-stage respiratory disease: severe PH + COPD or ILD  PAH: consider transplant when progressive disease requires parenteral therapy  Defer until deterioration occurs despite max medical Rx  Double lung transplantation: preferred procedure for PAH  Reduces right ventricular afterload: right heart often recovers  PAH: 23% unadjusted 3-mo mortality after procedure  Heart-lung transplantation  For uncorrectable congenital heart lesions  For concomitant primary cardiac failure

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. What is the role of exercise?  Exercise improves exercise capacity and QOL  Important adjunct to medical therapy  Avoids deconditioning from being sedentary  PH isn’t a contraindication to judicious exercise  Encourage patients to remain active within symptom limits  Mild breathlessness is acceptable  Avoid severe breathlessness, exertional dizziness, near syncope, or chest pain  Isometric exercises discouraged due to exertional syncope

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. CLINICAL BOTTOM LINE: Treatment…  Right HF  Use diuretics, salt restriction  PH due to left heart or chronic hypoxemic lung disease  Treat underlying disorders (not PH per se)  Chronic thromboembolic PH  Use anticoagulants + possible thromboendarterectomy  PAH  Perform right heart catheterization with vasodilator test  Don’t treat empirically with calcium-channel blockers  Advanced therapies: prostacyclins, endothelin-receptor antagonists, PDE5 inhibitors  Evaluate need for supplemental oxygen  Lung transplantation: in nonresponsive advanced disease

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. What is the prognosis of PH?  Negative prognostic sign in many conditions (HF, COPD)  In particular, PAH prognosis  Worse in presence of advanced NYHA/WHO functional class, shorter 6-min walking distance  Worse with connective tissue disease  Worse with portopulmonary hypertension  Untreated PAH: median survival 2.8 years

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. What should patients be taught about pulmonary hypertension?  How PH is distinct from systemic hypertension  How PH often connotes significant systemic disease  Regardless of the cause  Requires ongoing closely coordinated medical care  Requires monitoring salt intake, fluid balance, weight  That patients with PAH may need to…  Self-administer medications  Monitor themselves for AEs or progression of disease  Know how other health issues might compromise PAH care  Where to find information and peer support

© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (3): ITC2-1. CLINICAL BOTTOM LINE: Prognosis…  PH a negative prognostic sign in many conditions (HF, COPD)  Treatment can delay complications  Ongoing closely coordinated medical care is important  Monitor salt intake, fluid balance, weight  PH almost always connotes significant systemic disease