Pulmonary Hypertension

Pulmonary Hypertension
…the other high blood pressure
Michael J. Krowka, MD
Division of Pulmonary and Critical Care
Mayo Clinic
Jauch Symposium, Waterloo Iowa
May 18, 2012

Current Issues to discuss
► Diagnostics
• New Classification
• New Diagnostic Criteria
• Pulmonary artery hypertension vs pulmonary venous hypertension
► Pulmonary Artery Hypertension (PAH) Therapy update
• The treatment options…$$$
► Specific Family Practice considerations

Pulmonary Hypertension (PH)
Concept…
…increased blood pressure in the
pulmonary vascular bed
Pulmonary artery hypertension (PAH)? or
….Pulmonary venous hypertension (PVH) or
…both?

Pulmonary Artery Hypertension:
The overall concept…
A pulmonary arterial vascular obstructive process*… with
variable presence of vasoconstriction…
* endothelial proliferation
smooth muscle proliferation
in-situ thrombosis
fibrosis
platelet aggregates
plexogenic change

Pulmonary Hypertension Classification
►1973 Geneva
• Primary pulmonary hypertension (PPH) vs secondary pulmonary hypertension
►1998 Evian
• 5 Subgroups of pulmonary hypertension
• Pulmonary artery vs pulmonary venous hypertension
►2003 Venice
• Abandon term PPH – use “idiopathic Pulmonary Artery Hypertension” (IPAH)
►2008 Dana Point
• Add hematologic diagnoses (hemolytic anemias/splenectomy)
►2013 Nice
• Revisions??

Pulmonary Artery Hypertension (PAH)
Consequence…
…right heart failure and death

Classification of
Pulmonary
Hypertension (PH)
Summer, 2009
I. Pulmonary artery hypertension
(PAH)
II. PH owing to left heart disease
III. PH owing to lung
disease/hypoxemia
IV. PH due to chronic pulmonary
emboli
V. PH with unclear/multifactorial
etiology

Group I - Pulmonary Artery Hypertension
Dana Point 2008
I. Pulmonary artery hypertension - PAH
1.1 Idiopathic
1.2 Heritable
a.BMPR2
b. ALK1
1.3 Drugs and Toxins
1.4 Associated with
1.4.1 connective tissue disease
1.4.2 HIV infection
1.4.3 portal hypertension
1.4.4 congenital heart disease
1.4.5 schistosomiasis
1.4.6 chronic hemolytic anemia
Importance?...
…insurers will pay for Group I

The Diagnostic Criteria for Pulmonary Artery
Hypertension
Right heart catheterization...
• Mean Pulmonary Artery Pressure (MPAP) > 25 mm Hg
• Pulmonary Artery Occlusion Pressure (PAOP) < 15 mm Hg
• Pulmonary Vascular Resistance (PVR) > 240 dynes.s.cm -5
where PVR = (MPAP-PAOP) * 80
CO

Common Pulmonary Hemodynamics
Associated with Pulmonary Hypertension
MPAP PVR CO PAOP
► Hyperdynamic
Circulatory State
(Anemia, Liver disease)
► Excess Volume
(Left heart dysfunction)
► Vasoconstriction
with vasoproliferation
(IPAH, POPH)

Screening for Pulmonary Hypertension
Procedure of choice…
• Transthoracic Doppler Echocardiography
• Goals:
– estimate right ventricular systolic pressure (RVSP)
– determine RV size/function

Echocardiographic Features of Pulmonary Hypertension
TR=Tricuspid Regurgitant
Peak Velocity (m/sec)
Dp= 4(TR) 2
RVSP = RA est + Dp
Barnett, C. F. et al. JAMA 2008;299:324-331.
Copyright restrictions may apply.

PH diagnosis via right heart
catheterization (RHC)
Measure
MPAP- mean pulmonary artery pressure
CO - cardiac output
PAOP - pulmonary capillary wedge pressure
Calculate
PVR - pulmonary vascular resistance

Key points regarding Doppler
echo...
►RVSP is an estimate of the pulmonary artery
systolic pressure*
►Normal RVSP < 35- 40 mmHg
►But remember…the definition of PH is based
upon mean pulmonary artery pressure
*Assumes pulmonary valve is normal

Signs and symptoms of PH
►Nothing is “pathognomonic”
►Early - exertional dyspnea
►Late
• chest pain
• chest pressure
• leg edema
• abnormal ECG/CXR
• syncope

ECG findings of Importance
► RV and RA enlargement
► Tall P waves II, III, aVF
► Right axis
► ST depression and T wave
inversion V1-V4 suggests severe
PAH
Chest 1997;111:537-43

Caveat
►An open lung biopsy to diagnose the
“cause” of pulmonary hypertension?
…risky business
…rarely done
…don’t do it

3 Treatment Pathways
Block
Enhance
Enhance

Current PAH Medication Options
• Ca ++ Channel Blocker X
Mild Moderate Severe
25

IV Prostacyclins
► Prostacyclin (PGI 2 )
► pulmonary vasodilator
• inotropic effect
• inhibits platelet
aggregation?
• antiproliferation?
► continuous 24 hour
infusion
► most experience

…other therapeutic options
►If all meds fail…
• atrial septostomy
• off loads RV
…but creates R→L shunt (and hypoxemia)
• organ transplantation
►heart-double lung
►double lung

Treatment Success?
► Hemodynamics
• Doppler Echo
► ↓ RVSP
• Right heart cath
► ↓ MPAP
► ↓ PVR
► ↑ CO
• Right ventricular
size/function
► Survival
► Surrogate Markers
• Pro-BNP (B-type natriuretic
peptide)
• Uric Acid
• 6 Minute walk
• Quality of life
• Symptoms

Family practice considerations…
Survival data…REVEAL Registry publicatiions
…a few comments
►Elderly…PAH vs PVH
►Syncope
►DVT (and what may follow)
►Pregnancy
►“Lets stop at McDonalds”
►The neighborhood alcoholic
►“Good night Irene”

N = 3,500

DVT x2…5 years later…

AJRCCM
2011; 183: 1605-13
►CTEPH frequency?
►Risk?
► .57- 3.8% of those surviving acute PE
►~ 66% have no previous PE history
• Recurrent DVT
• RVSP > 50 mmHg at time of PE
• Myeloproliferative disorders
• Indwelling catheters/ventriculoatrial shunts
• Splenectomy
• Hypercoagulable states (Antiphospholipid antibody syndrome)

Pregnancy and PAH
►A fatal combination
• 30-56% maternal mortality over the years
• Mortality usually within 4 weeks of delivery
►Early counseling of PAH women
►Use Referral Centers
►IV prostacyclin or oral phosphodiesterase
inhibitors

N=73
IPAH =29
CHD = 29
Other = 15
Maternal death 18/73 (25%)
Primigravidae highest risk
ERAs teratogenic

All C-section
Sildenafil use
2 maternal deaths
intraop
2 weeks postop

Obesity and PH

…massive ascites
due to alcoholic cirrhosis

Portopulmonary hypertension
► PAH as a consequence of portal hypertension
• 3 rd most common reason for referral to PH Clinics

REVEAL Registry 5-year survivals
Chest 2012; 139:1285-1293
IPAH: 64%
POPH: 40%

Overnight Pulse Oximetry

Newest ideas in PAH Treatment
►Identify genetically susceptible individuals
►Initiate “preventive” therapies
• Anti-platelet aggregation
• Inhibition of growth factors
► Prostacyclin receptor agonists (oral)
► Tyrosine kinase inhibitors (Imatinib)
► Rapamycin

Mayo PH Clinic
Daily appts (MD/Self referral)
6 Cardiologists
2 Pulmonologists

PHAssociation.org

In Summary...
► New onset exertional dyspnea…think PH
• Not uncommon in FP setting
► Screen by Transthoracic Doppler Echo
► Definitive diagnosis by right heart cath
• PAH versus PVH
► In PAH… oral vs inhaled vs SQ vs IV?
► selection a function of PAH severity (and $$$)
► Referral PH centers can be very helpful … “co-primary”
► Pulmonary Hypertension Association (PHA) Website
• excellent resource
... and sometimes we all are just plain “stuck” and have to ask for help…

Thank you