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

© Copyright Annals of Internal Medicine, 2011

Ann Int Med. 155 (3): ITC2-1.