Pulmonary Hypertension:
Management Update
Robert Vassallo, MD
Division of Pulmonary and Critical Care Medicine
Mayo Clinic, Rochester, MN.
KUWAIT 2014
Disclosures
• I have nothing to disclose with
respect to this presentation.
Key objectives of this presentation
• Review WHO updated classification of
pulmonary hypertension.
• Review diagnostic approach and caveats with
testing for pulmonary hypertension.
• Outline a clinical rationale for the
management of pulmonary hypertension.
• Discuss situations when expert opinion and
referral to specialized centers may be
necessary.
Pulmonary Hypertension
Concept…
…progressive increase in the blood
pressure in the pulmonary vascular bed
Consequence…
…right heart failure and death
Criteria for Pulmonary
Hypertension
• Mean Pulmonary Artery Pressure
MPAP > 25 mmHg at rest with
pulmonary capillary wedge pressure
≤15 mm Hg
4th World Symposium on Pulmonary Hypertension, Dana Point, CA 2008
Potential sites to induce
Pulmonary Hypertension
Pre-capillary
Post-capillary
Updated Clinical Classification of
Pulmonary Hypertension
1. Pulmonary arterial hypertension (PAH)
1. idiopathic (“primary pulmonary hypertension”)
2. secondary to systemic disorders
2. Pulmonary hypertension due to left heart disease
(pulmonary venous hypertension)
3. Pulmonary hypertension associated with respiratory
disease and/or hypoxia
1. COPD, Interstitial lung disease, OSA
4. Chronic thromboembolic/embolic pulmonary
hypertension
5. Pulmonary hypertension from unclear mechanisms
Journal of the American College of Cardiology
Vol. 62, No. 25, Suppl D, 2013
Mean pulmonary artery pressure and
cardiac output relationship
90
Severe
Mild to moderate
60
Mean PA
pressure
Normal
30
0
REST
0
EXCERCISE
5
10
15
Cardiac Output [L/min]
20
Signs and symptoms of
Pulmonary Hypertension
• Symptoms and signs are usually not
specific; delay in diagnosis very
common.
• Early – dyspnea with activity.
• Late symptoms:
•
•
•
•
syncope
chest pain / chest pressure
leg edema (signs of right heart failure)
abnormal findings on chest X ray or ECG
Diagnostic studies:
Chest radiography
Radiographic findings are subtle and often missed
ECG abnormalities
•
•
•
•
Right heart strain (RVH and RA enlargement)
Non-specific
Right axis deviation
ST depression and T wave inversion V1-V3
Screening for pulmonary
hypertension
• There is no perfect screening tool.
• Transthoracic echocardiography
• Goals:
• 1. determine right ventricular size
and systolic function
• 2. estimate right ventricular systolic
pressure
Diagnostic testing:
Trans-thoracic echocardiography
PASP = (4 x [TRV]2) + RAP
LA
RA
Echocardiography
uses Doppler
ultrasound to
estimate the
pulmonary artery
systolic pressure
LV
RV
Echo transducer
CP900234-1
Pulmonary hypertension diagnosis via
right heart catheterization
From Mayo Clinic Right Heart Catheterization Training Manual – Cardiology Rotation
Clinical approach to suspect
pulmonary hypertension
• If the echocardiogram suggests the
presence of pulmonary hypertension
• 1. perform careful evaluation for
secondary causes
• 2. consider whether you should
proceed to right heart catheterization
Once you have identified pulmonary
hypertension, look for causes
1. Pulmonary arterial hypertension (PAH)
1. idiopathic (“primary pulmonary hypertension”)
2. secondary to systemic disorders
2. Pulmonary hypertension due to left heart disease
(pulmonary venous hypertension)
3. Pulmonary hypertension associated with respiratory
disease and/or hypoxia
1. COPD, Interstitial lung disease, OSA
4. Chronic thromboembolic/embolic pulmonary
hypertension
5. Pulmonary hypertension from unclear mechanisms
Journal of the American College of Cardiology
Vol. 62, No. 25, Suppl D, 2013
Once pulmonary hypertension is
detected, look for causes!
European Heart Journal (2009) 30, 2493–2537









History and Exam
LFT, CBC
Autoimmune screen
Overnight oximetry
Echocardiography
Chest CT
V/Q scan
PFT
HIV serology
 Other testing as suggested
by H&P
European Heart Journal (2009) 30, 2493–2537
PAH (Group 1) Medication Options
Mild
25 <MPAP< 35
Moderate
Severe
35 <MPAP< 50
MPAP> 50
• Ca++ Channel Blocker
X
• Endothelin antagonist
X
X
• PDE-5 inhibitor
X
X
• Prostanoids
• Inhaled iloprost
• SQ treprostinil
• IV epoprostenol
X
X
X
X
X
X
X
X
Group 1: “Primary” pulmonary
arterial hypertension
• Remember PAH (Group 1) and PH (Groups
2-5) are different entities
• PAH is a progressive disease with a 50%
survival at 2.8 years
• Can lead to sudden death
• Often affects young adults: mean age 45
years
• Rarely familial
Group 1: Secondary pulmonary
artery hypertension
• Collagen vascular disease
• scleroderma
• Systemic lupus erythematosus
• Liver disease
• Congenital heart
• Drugs/toxins
• HIV infection
Therapy
•
•
•
•
Treat any underlying disease.
Treat cardiac disease (left sided).
Treat lung disease and hypoxemia.
Treat obstructive sleep apnea or any
associated sleep disorder.
• Treat thromboembolic disease.
• Remember: Groups 2-5 are managed
differently and vasodilator therapy is NOT
recommended.
Intravenous Vasodilators
Pulmonary Arterial
Respiratory Disease
Pulmonary Venous
Increased Shunt
Pulmonary Edema
Adjunctive therapy
• Salt restriction.
• Diuretics as needed.
• Oxygen at rest or with activity.
• Flu and pneumococcal vaccination.
• Digoxin ? Role if any.
• Anticoagulation ?
Group 1 PAH therapy
Drug of choice?
• Right heart catheterization
vasodilator “challenge”
• 20% acute drop in MPAP and PVR?
...begin with ca++ channel blocker
Right Heart Catheterization and
Vasodilator Trial
Acute Responder
Non-Responder
NYHA II-IV
Calcium Channel Blocker
Vasodilator therapy ERA or PDE5-inh
or prostacyclin analog
Not Improved
Involve a specialist
with expertise
Consider combination
therapy
Transplant
Improved
Calcium Channel Blockers
• PAH therapy is based on severity of
disease as determined by right heart
catheterization and responsiveness to
vasoactivity testing.
• Although not FDA approved for the
treatment of PAH, CCBs commonly
used are nifedipine, diltiazem, and
amlodipine.
• All agents are titrated to clinical effect.
Objective measures to monitor
therapy…every 3-6 months
• 6 minute walk (goal > 300 meters)
• NT-ProBNP (Brain Naturetic Peptide)
• Sequential echocardiography
• Other studies depending on context
…other therapeutic options
• If chronic pulmonary emboli…
• pulmonary thromboendarterectomy
surgery
• If all meds fail…
• atrial septostomy
• organ transplantation
• heart-double lung
• double lung
Riociguat (a stimulator of soluble guanylate cyclase)
significantly improved exercise capacity and pulmonary
vascular resistance in patients with chronic
thromboembolic pulmonary hypertension.
N Engl J Med 2013;369:319-29.
Final “take home” messages
• New onset exertional dyspnea…think of pulmonary
hypertension.
• Screen by Transthoracic Doppler Echo but make sure
you tell the cardiologist that you are thinking of PH!
• Definitive diagnosis by right heart catheterization.
• Several pharmacologic options now available:
selection a function of PAH severity, expertise, cost
assessment, and other factors.
• Pregnancy may cause significant challenges.
• PH patients are increasingly older with potential
multiple ongoing diagnoses.
Thank you so much for
the invitation.