Suspecting Pulmonary Hypertension in The Dyspneic Patient: Who, When, and How

Suspecting Pulmonary Hypertension
in the Dyspneic Patient:

Who, When, and How
New York, New York
October 21, 2013

Who, When, and How
Host:
Kenneth J. Steier, DO, FACOI, FCCP, MBA, MPH, MHA, MGH
Guest Presenter:
Arunabh Talwar, MD, FCCP

Who, When, and How
Host:
Kenneth J. Steier, DO, FACOI, FCCP, MBA, MPH, MHA, MGH

Dean, TouroCOM-Middletown Campus
Clinical Dean, TouroCOM-Harlem Campus
Internal Medicine, Pulmonary and Critical Care
Touro College of Osteopathic Medicine
New York, New York
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This live activity has been planned and implemented in accordance with the Essential
Areas and Policies of the Accreditation Council for Continuing Medical Education
(ACCME) through the joint sponsorship of Washington University School of Medicine,
Continuing Medical Education and the Pulmonary Hypertension Association.
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maximum of 1.5 AMA PRA Category 1 Credits.
Physicians should claim only the credit commensurate
with the extent of their participation in the activity.
Faculty Disclosure
Dr. Steier has [to be added]
Dr. Talwar has no relevant financial relationships to disclose.
Lets get started

Who, When, and How
Guest Presenter:
Arunabh Talwar, MD, FCCP
Associate Professor of Clinical Medicine
Albert Einstein College of Medicine
Director, Pulmonary Hypertension and Interventional Bronchoscopy Program
North Shore University Hospital
Manhasset, New York
The Pulmonary Hypertension Association (PHA)

is the leading non-profit organization for PH
research, public awareness, and services. The
organization has over 12,000 members, including
patients, family members, and medical
professionals.
www.PHAssociation.org
Case Presentations
2 Women With Dyspnea

Patient 1
Patient 2

Patient 1
Patient 2
Age: 57 years
Age: 48 years
Comorbidities:
Comorbidities:
HTN
HTN
Diabetes
CKD
CKD
Systemic sclerosis
Atrial fibrillation

Patient 1
Patient 2
NYHA Class III
NYHA Class III
BP: 172/65 mm Hg
BP: 120/84 mm Hg
JVP elevated
JVP elevated
Irregularly irregular
Regular rate, rhythm
Loud P2
Loud P2
2/6 murmur
(holosystolic,
left sternal border)
3/6 murmur
(holosystolic,
left sternal border)
2+ leg edema
2+ leg edema
Pulmonary Arterial Hypertension (PAH):

Key
Average
14-mo delay from initial presentation to
Points
diagnosis: need to diagnose early
Evaluation must be methodical and include
echocardiography and right heart catheterization
To treat effectively and avoid harm, PAH must be
differentiated from pulmonary venous hypertension
Prognosis improves with therapy, but PAH remains a
progressive fatal disease
Therapies and management strategies continue to
evolve
Hemodynamic Definition of PH/PAH
PH
PAH
Mean PAP 25 mm Hg
Mean PAP 25 mm Hg plus
PCWP/LVEDP 15 mm Hg
ACCF/AHA includes PVR >3 Wood Units

Badesch D et al. J Am Coll Cardiol. 2009;54:S55-S66.
Gali N et al. Eur Heart J. 2009;30:2493-2537.
McLaughlin VV et al. J Am Coll Cardiol. 2009;53:1573-1619.
Clinical Classification of Pulmonary

Hypertension (Dana Point)
1. PAH
Idiopathic PAH
Heritable
Drug- and toxin-induced
Persistent PH of newborn
Associated with:
CTD
HIV infection
portal hypertension
CHD
schistosomiasis
chronic hemolytic anemia
3. PH Owing to Lung Diseases and/or Hypoxia

COPD
ILD
Other pulmonary diseases with mixed
restrictive and obstructive pattern
Sleep-disordered breathing
Alveolar hypoventilation disorders
Chronic exposure to high altitude
Developmental abnormalities
4. CTEPH
1. PVOD and/or PCH

2. PH Owing to Left Heart Disease
Systolic dysfunction
Diastolic dysfunction
Valvular disease
5. PH With Unclear Multifactorial Mechanisms

Hematologic disorders
Systemic disorders
Metabolic disorders
Others
Simonneau G et al. J Am Coll Cardiol. 2009;54;S43-S54.
PH Lessons
1.
Pulmonary Hypertension Is Common
2.
WHO Group I PAH Is Rare but Deadly

Make the Diagnosis Early
3.
Know the PH Clinical Clues in the Dyspneic

Patient
4.
Look Beyond the PA Pressure on

Echocardiography
5.
Definitive Diagnosis of PAH Requires Invasive

Hemodynamic Testing
PH Lessons (contd)
6.
Always Look for the Underlying Cause of PH
7.
Treatment of PHGet the Diagnosis Correct

and Determine Functional Status
8.
Lack of Response to Acute Vasodilator

Challenge in PAH Untreatable
9.
First Do No HarmLearn to Differentiate WHO

Group I PAH From Other Forms of PH
10. Appropriate, Timely, and Collaborative Care:

Key to Early and Effective Treatment of PH in
the Dyspneic Patient
Lesson 1
Pulmonary Hypertension
Is Common
PH in the Community: PASP and Survival

All Participants
(N=1413)
No Cardiopulmonary Disease
(N=778)
Overall Log Rank p<0.001
Overall Log Rank p=0.002

1.000
Cumulative survival
Cumulative survival
1.00
0.95
0.90
PASP quintile
1: 15-23 mm Hg
2: 24-25 mm Hg
3: 26-29 mm Hg
4: 30-32 mm Hg*
5: 34-66 mm Hg*
0.85
0.975
PASP tertile
1: 15-24 mm Hg
2: 24-28 mm Hg
3: 28-43 mm Hg*
0.950
0.925
0.900
Time (yr)
Time (yr)
Uptoto20%
20%ofofthe
theUS
USpopulation
populationhas
hasecho
echo
Up
evidenceofofPH
PH
evidence
*Bonferroni-adjusted p<0.05 in pairwise comparison with lowest tertile.
Lam CSP et al. Circulation. 2009;119:2663-2670.
Epidemiology of PH by Echo
Single echo lab / Australian community of 165,450
Etiology of PH noted on echocardiogram
PAH, 2.7%
Unknown,
15.4%
CTEPH, 2.0%
Lung disease,
Sleep-related
hypoventilation,
9.3%
Miscellaneous, 2.7%
N=936 of 10,314 patients with echo PASP >40 mm Hg.
Strange G et al. Heart. 2012;98:1805-1811.
Left heart
disease, 67.9%
PH Is Common in Elderly Patients With

Heart Failure With Preserved EF
heart failure with preserved
EF: 83% with PH
HTN but no CHF (control):
8% with PH
100
Cumulative (%)
PH by echo in a communitybased sample:
50
25
0
Patients with PH:
larger LA size
higher E/e ratio
Lam CS. J Am Coll Cardiol. 2009;53:1119.
HTN
HFpEF
10
30
50
70
90
PASP (mm Hg)
PH prevalence (%)
older
higher systolic BP
p<0.001
75
100
83
75
50
25
0
p<0.001
8
HTN
HFpEF
110
Lesson 2
WHO Group I PAH Is Rare

but Deadly
Make the Diagnosis Early
Idiopathic PAH: Survival If Untreated
Percentage surviving
100
80
NIH registry
Sitbon historical control
ACCP estimate
Incidence: 2-6 cases per

million in US
Poor prognosis in an era
lacking therapy
60
Therapeutic options and

research efforts now offer
more hope
40
20
0
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5
Years of follow-up
Adapted from: Sitbon O et al. J Am Coll Cardiol. 2002;40:780-788. DAlonzo GE et al. Ann Intern Med.
1991;115:343-349. McLaughlin VV et al. Chest. 2004;126:78S-91S.
French Registry: Kaplan-Meier Survival Estimates

in Combined PAH Population vs NIH-predicted
100
Observed
80
Survival
(%)
60
Predicted (NIH Registry)
40
20
0
No. at risk:
All patients
12
24
36
Time (mo)
56
69
98
Humbert M et al. Circulation. 2010;122:156-163.
113
120
127
133
Schematic Progression of PAH

Presymptomatic/
Compensated
Symptomatic/
Decompensating
Declining/
Decompensated
CO
Symptom Threshold
PAP
Right Heart
Dysfunction
PVR
CO=
TPG
PVR
TPG=transpulmonary gradient.
Time
Percent of patients FC III/IV at diagnosis
Advanced Functional Class at

Diagnosis Common and Indicates
Delayed Recognition
100
Approximate prevalence: 15 cases/million

80
More
common in women
Spans
broad age range
60
Delay in diagnosis persists
40
Most patients diagnosed with late symptoms

20
Poor
prognosis if untreated (median survival <3 yr)
0
REVEAL Registry
(N=1831)
NIH Registry
(N=187)
French Registry
(N=674)
Badesch DB et al. Circulation. 2010;137:376-387. DAlonzo GE. Ann Intern Med. 1991;115:343-349.
Humbert M et al. Am J Respir Crit Care Med. 2006;173:1023-1030.
Lesson 3
Know the PH Clinical Clues

in the Dyspneic Patient
Is There a Reason to Suspect PAH?

Clinical Presentation
History
Dyspnea (86%)
Fatigue (27%)
Chest pain (22%)
Edema (22%)
Syncope (17%)
Dizziness (15%)
Cough (14%)
Palpitations
(13%)
Exam (PH)
Exam (RV Failure)
Loud P2 (listen at apex)

RV lift (left parasternal
fingertips)
RV S3, S4
Systolic murmur (TR;
inspiratory augmentation)
Early systolic click
Midsystolic ejection
murmur
Diastolic murmur (PR)
JVD; increased A
wave, V wave;
hepatojugular reflex
Pulsatile liver
Hepatomegaly
Edema
Ascites
Low BP, low PP, cool
extremities
REVEAL. Brown LM et al. Chest. 2011;140:19-26.

Adapted from McLaughlin VV et al. J Am Coll Cardiol. 2009;53:1573-1619.
Patient Presentation: Nonspecific

Symptoms
Dyspnea
Fatigue
Near syncope/syncope
Chest pain
Palpitations
Edema
0 10 20 30 40 50 60 70
Patients (%)
Median Time From Symptom Onset to Diagnosis

NIH Registry (1981 to 1985) 1.3 years
REVEAL Registry (2006 to 2007) 1.1 years
Rich A et al. Ann Intern Med. 1987;107:216-223.
Badesch DB et al. Chest. 2010;137:376-387.
Multiple
educational
efforts

Risk Factors
Family history
Connective tissue disease
Congenital heart disease
Portal hypertensionorthotopic liver transplant
candidate
Environmental/drug factors
HIV

ECG
Right Axis
Right
Atrial
Enlargement
RVH
RV Strain

Chest X-ray
Normal
Abnormal
Peripheral hypoPeripheral
hypovascularity
(pruning)
vascularity (pruning)
Prominent central
Prominent
central
pulmonary
artery
pulmonary artery
Adapted from McLaughlin VV et al. J Am Coll Cardiol. 2009;53:1573-1619.
RV enlargement
RVinto
enlargement
retrosternal
into
retrosternal
clear space
clear space

Echo
RV enlargement
RA enlargement
Septal straightening
Loss of IVC inspiratory collapse
Tricuspid regurgitation
Pericardial effusion
Decreased RV systolic dysfunction
TAPSE (tricuspid annular plane systolic
excursion)
TAPSE 2.3 cm
TAPSE 1.5 cm
Relatively preserved
RV function
RV dysfunction
McLaughlin VV et al.
J Am Coll Cardiol.
2009;53:1573-1619.

Evaluation for CTEPH
Not a PAH subgroup, but:
Should not be missed
Is potentially curable with thromboendarterectomy (PEA)
3% to 4% of acute PE do not entirely resolve
One half of those with CTEPH do not have an apparent
history of acute PE
Normal VQ scan excludes chronic PE
CT angiogram can detect chronic clot (but the radiologist
should be experienced when interpreting the imaging
distal disease can be subtle)

VQ Scan
Idiopathic
Pulmonary
Arterial
Hypertension
Chronic
Pulmonary
Embolism
CTEPH: CT Angiogram
web or bands
stenosis
recanalization
fresh
thrombus
retraction with
partial obstruction
retraction with
total obstruction
Disturbed resolution of thrombus*
PEA
PEA
*Castaer E et al. Radiographics. 2009;29:31-53.
Less
Less
subtle
subtle
thrombus
thrombus

Pulmonary Function
Underlying lung disease (diagnostic group III)
Abnormalities consistent with PH
IPAH and CTEPH
Systemic Sclerosis
20% have an isolated reduction

in DLCO
20% have an isolated reduction

in DLCO
DLCO mildly reduced

(60%-80% predicted NIH registry)
Severity predicts future PAH
PVR correlates with reduction in

DLCO
DLCO correlates inversely with

PASP
DLCO=diffusing capacity of the lungs for carbon monoxide

Overnight Oximetry
Hypoxia may signal underlying sleep apnea
In patients with obstructive sleep apnea (OSA),
pulmonary artery pressures (PAP) are reported to
decrease in response to CPAP therapy
Untreatedresponse to other treatment likely to be
less effective
Somers VK et al. J Am Coll Cardiol. 2008;52:686-717.
Screening Guidelines: Patients With

Known PAH Risk
Substrate
Further Assessment
Rationale
Known BMPR2
mutation
Echo yearly; RHC if echo shows

evidence of PAH
Early PAH detection; 20%

chance of developing PAH
Systemic
sclerosis*
Echo yearly; RHC if echo shows

evidence of PAH
8% prevalence of PAH
HIV
Echo if symptomatic; RHC if echo

shows evidence of PAH
0.5% prevalence of PAH
Portal
hypertension
Echo if OLT considered; RHC if

echo shows evidence of PAH
4% prevalence of PAH;
predictive of poor outcome
Congenital
heart disease
Echo and RHC at diagnosis;

consider repair of L-R shunt defect
High PAH probability if

unrepaired (Eisenmenger)
*Systemic sclerosis: consider echocardiogram if
% FVC
% DLCO
>1.6 or unexplained declining DLCO.
Diagnostic Algorithm for PH

Identical for local practitioners and PH specialists
Requirements:
thorough evaluation
high quality studies and interpretation
Establish a suspicion of PAH
Confirm the diagnosis (right heart catheterization)
Classify the type of PH (Group I-V)
Determine the disease severity
Select the appropriate treatment for patients with PAH
Pivotal Tests
Contingent Tests
ACCF/AHA Diagnostic Algorithm
History
Exam
CXR
ECG
Echocardiogram
Index of Suspicion of PH
TEE
Exercise Echo
VQ Scan
Pulmonary Angiography
Chest CT Angiogram
Coagulopathy Profile
PFTs
ABGs
Overnight
Oximetry
Polysomnography
Other CTD Serologies
Ventilatory Function
Gas Exchange
Sleep Disorder
Scleroderma, SLE, RA
Establish Baseline
Prognosis
Functional Test
(6MWT, CPET)
McLaughlin VV et al. J Am Coll Cardiol.

2009;53:1573-1619.
Chronic PE
Portopulmonary Htn
LFTs
RH Cath
RVE, RAE, RVSP, RV

Function
Left Heart Disease
VHD, CHD
HIV Infection
HIV
ANA
Contribute to
Assessment of:
Vasodilator Test
Exercise RH Cath
Volume Loading
Left Heart Cath
Confirmation of PH
Hemodynamic Profile
Vasodilator Response
Lesson 4
Look Beyond the PA Pressure

on Echocardiography
The Right Ventricle in PAH

RV pressure/volume overload
RV failure
Progressive structural changes in the RV

due to poor adaptation to increasing PVR
RA
LA
RV
LV
Cross section
PAH: RV Changes
LV
RV
LA
RA
TTE apical
4-chamber view
Normal
PH
Echocardiography in PH
Strengths
Best screening tool for PH
Inexpensive, portable, readily
available, non-invasive, no
radiation
Allows for serial assessment
Provides clues to other
diagnoses (eg, LHD, CHD)
Limitations
Experienced techs/MDs
essential
Imaging quality suboptimal in
patients with poor windows
(eg, lung disease, obesity)
Right ventricle not imaged
adequately in some labs
TR jet inadequate to
determine RVSP in
10%25% of patients

Bossone E et al. Chest. 2005;127:1836-1843.
Brecker SJ. Br Heart J. 1994;72:384-389.
Essential Components of the

Echocardiogram in PH
Doppler estimate of RVSP
Assess biventricular size and systolic function
Look for interventricular septal shift
Discriminate between pulmonary arterial and pulmonary
venous causes of PH (if possible)
Assess for congenital heart shunt lesions
Document pericardial effusion

Key Features of PAH on Echo

Enlarged RV with normal or small LV
RA, RV, and PA enlargement
RV dysfunction
Increased RVSP
Interventricular septal flattening during systole
diastole
Mitral E/A wave ratio <1.0
Estimation of RV Systolic Pressure

(RVSP)
IVC Collapse PH.avi
RVSP = 4(velocity of TR)2 + RA pressure

= 4(4)2 + 20
= ~84 mm Hg
Mild PAH
Systole in short-axis view
Apical 4-chamber view
RV
IVS
Mild PAH56.avi
Mild PAH20.avi
LV
Diastole in short-axis view
Mild PAH20.avi
TR jet
Moderate PAH Disease

Moderate PAH16.avi
Moderate PAH16.avi
Moderate PAH 31
TR jet
Severe PAH and RV Failure

Severe PAH29.avi
Severe PAH 34.avi
Severe PAH29.avi
TR jet
Lesson 5
Definitive Diagnosis of PAH

Requires Invasive
Hemodynamic Testing
Diagnostic Cardiac Catheterization

Establish the presence of PH
Make the diagnosis of PAH
measure wedge pressure and/or LVEDP
Determine severity and prognosis of disease
Exclude congenital heart disease
Perform acute vasodilator test
Catheterizationisisrequired
requiredwhen
whenpulmonary
pulmonary
Catheterization
hypertensionisissuspected
suspected
hypertension
PH: The Importance of Hemodynamics

Pulmonary venous hypertension
Elevated PCWP, normal PVR
VC
RA
RV
PA
PV
LA
LV
Ao
PC
PAH
PH with respiratory disease
CTEPH
Normal PCWP, elevated PVR
Other:
Other:
high CO
high CO
PH: Define the Lesion

(mean PAP 25 mm Hg)
Post-capillary PH
PCWP >15 mm Hg
PVR <3 Wood units
RA
RV
PA
PC
PV
LA
LV
Ao
Mixed PH
PCWP >15 mm Hg
PVR 3 Wood units
Pre-capillary PH
PCWP <15 mm Hg
PVR 3 Wood units
Other:
High CO
PCWP <15 mm Hg
PVR <3 Wood units
Lesson 6
Always Look for the

Underlying Cause of PH
Pivotal Tests
Contingent Tests
ACCF/AHA Diagnostic Algorithm
History
Exam
CXR
ECG
Echocardiogram
Index of Suspicion of PH
TEE
Exercise Echo
VQ Scan
Pulmonary Angiography
Chest CT Angiogram
Coagulopathy Profile
PFTs
ABGs
Overnight
Oximetry
Polysomnography
Other CTD Serologies
Ventilatory Function
Gas Exchange
Sleep Disorder
Scleroderma, SLE, RA
Establish Baseline
Prognosis
Functional Test
(6MWT, CPET)
McLaughlin VV et al. J Am Coll Cardiol.

2009;53:1573-1619.
Chronic PE
Portopulmonary Htn
LFTs
RH Cath
RVE, RAE, RVSP, RV

Function
Left Heart Disease
VHD, CHD
HIV Infection
HIV
ANA
Contribute to
Assessment of:
Vasodilator Test
Exercise RH Cath
Volume Loading
Left Heart Cath
Confirmation of PH
Hemodynamic Profile
Lesson 7
Treatment of PHGet the
Diagnosis Correct and
Determine Functional Status
Mechanisms of Action of Approved

Therapies for PAH
Endothelin
Pathway
Endothelial cells
Pre-proendothelin
Nitric Oxide
Pathway
Endothelial cells
Arachidonic acid
Proendothelin
L-arginine
Endothelin
receptor A
Prostacyclin
Pathway
L-citrulline
Endothelin-1
Endothelinreceptor
antagonists
Endothelin
receptor B
Vasoconstriction
and proliferation
Prostaglandin I2
Prostacyclin (prostaglandin I2)

Nitric Oxide
cGMP
Exogenou
s nitric
oxide
SCG
stimulator
cAMP
Vasodilation
and antiproliferation
Phosphodiesterase
type 5
Vasodilation
and antiproliferation
Phosphodiesterase
type 5 inhibitor
Smooth muscle cells
Humbert M et al. N Engl J Med. 2004;351:1425-1436.
Smooth muscle cells
Prostacyclin
derivatives
PAH Treatment Goals

Improve survival
Improve quality of life
Improve exercise
capacity
Prevent clinical
worsening
escalation of therapy
hospitalization
6MWD
lung transplantation
WHO functional
classification
death
Improve hemodynamics
Chronic Adjuvant Treatment

Digoxin
Variable inotropic effect and use
No long-term data; need to balance unproven benefits
with known risks
Oxygen
Use to prevent hypoxic vasoconstriction
Consider exercise, sleep, altitude
Aim for target saturation >90%
May not correct hypoxia with shunt
Badesch DB et al. Chest. 2007;131:1917-1928.
Chronic Adjuvant Treatment

Diuretics
Most patients need
Diuretics
Hypotension not a contraindication

Renal function and electrolytes
must be monitored closely
Poor CO
and hypotension
Observed Survival in IPAH Patients

With and Without Anticoagulation
Anticoagulation
100
Recommended in IPAH
INR goal 1.5 2.5

Fuster V et al. Circulation. 1984;70:580-587.
Badesch DB et al. Chest. 2004;126:35S-62S.
(60)
80
Observational data only

Need to balance unproven
benefits with known risks
Improved CO
and BP
Anticoagulation
(49)
60
Percent
surviving
(21)
(36)
40
(14)
20
0
No Anticoagulation
0
2
Years
(7)
PAH Therapy
(+) Vasodilator Response
Calcium channel blockers
() Vasodilator Response or Non-sustained
Endothelin receptor antagonists
Phosphodiesterase-5 inhibitors
SCG stimulator
Prostanoids
Choice of Therapy
Local Practitioners
Knowledge and management of comorbid illnesses
Geographically close to patients
Established therapeutic relationship
PH Centers
Experience with therapy escalation
Knowledge of drug-drug interactions; eg, PDE-5 inhibitors
and antiretroviral therapy
Nursing support for management of parenteral medications
Relationships with other subspecialists; eg, lung transplant
centers
Initial Therapy: Making the Right

Decision
Make sure the patient truly has PAH and not
another type of PH (especially pulmonary venous
hypertension)
Severity of disease
Patient preference
Trying to weigh the data
When comparing trials, examine objective
baseline characteristics (6MWD, hemodynamics)
PAH Determinants of Risk

LOWER RISK
DETERMINANTS OF RISK
HIGHER RISK
No
Clinical evidence of
RV failure
Yes
Gradual
Progression of symptoms
Rapid
II, III
WHO class
IV
Longer (>400 m)
6MWD
Shorter (<300 m)
Peak VO2 >10.4 mL/kg/min
CPET
Peak VO2 <10.4 mL/kg/min
Minimal RV dysfunction
Echocardiography
Pericardial effusion,
significant RV
enlargement/dysfunction;
RA enlargement
RAP <10 mm Hg;

CI >2.5 L/min/m2
Hemodynamics
RAP >20 mm Hg;

CI <2.0 L/min/m2
Minimally elevated
BNP
Significantly elevated
ACCF/AHA Consensus PAH Treatment

Algorithm (Modified)
Anticoagulate Diuretics
Anticoagulate Diuretics
Oxygen Digoxin
Oxygen Digoxin
Acute Vasoreactivity Testing

Acute Vasoreactivity Testing
Positive
Oral CCB
Oral CCB
Sustained
Sustained
Response
Response
Yes
Continue
Continue
CCB
CCB
No
Negative
Lower Risk
Lower Risk
Higher Risk
Higher Risk
ERAs or PDE-5 Is or SCG

ERAs or
PDE-5 Is or
SCG
stimulators
(oral)
stimulators (oral)
Epoprostenol or Treprostinil (IV)
Iloprost (inhaled)
Iloprost (inhaled)
Treprostinil (SC, inhaled)
Treprostinil (SC, inhaled)

Iloprost (inhaled)
Iloprost (inhaled)
ERAs or PDE-5 Is (oral)
ERAs or PDE-5 Is (oral)
Treprostinil (SC)
Treprostinil (SC)
Reassess: consider
Reassess: consider
combo-therapy
combo-therapy
Investigational Protocols
Investigational Protocols
Modified from McLaughlin VV et al. J Am Coll Cardiol. 2009;53:1573-1619.
Atrial septostomy
Atrial
septostomy
Lung
transplant
Lung transplant
Lesson 8
Lack of Response to Acute

Vasodilator Challenge in
PAH Untreatable
Acute Vasodilator Trial

Purpose:
identify vasodilator responders who are candidates
for CCB therapy
Short-acting vasodilators
inhaled nitric oxide is preferred
Definition of response
decrease in mPAP by 10 mm Hg down to
mPAP of 40 mm Hg
with improvement or maintenance of
cardiac output
Rubin LJ. Chest. 2004;126:4S-6S.
Sample Acute Vasodilator Responses

PATIENT A
PATIENT B
BASELINE
AFTER 40 PPM iNO
BASELINE
AFTER 40 PPM iNO
mPAP 45 mm Hg
mPAP 34 mm Hg
mPAP 45 mm Hg
mPAP 37 mm Hg
PCWP 10 mm Hg
PCWP 10 mm Hg
PCWP 10 mm Hg
PCWP 7 mm Hg
CO 5 L/min
CO 6 L/min
CO 5 L/min
CO 6 L/min
PVR 7 Wood units
PVR 4 Wood units
PVR 7 Wood units
PVR 5 Wood units
RESPONDER OR
NON-RESPONDER??
RESPONDER OR
NON-RESPONDER??
Sample Acute Vasodilator Responses

PATIENT A
PATIENT B
BASELINE
AFTER 40 PPM iNO
BASELINE
AFTER 40 PPM iNO
mPAP 45 mm Hg
mPAP 34 mm Hg
mPAP 45 mm Hg
mPAP 37 mm Hg
PCWP 10 mm Hg
PCWP 10 mm Hg
PCWP 10 mm Hg
PCWP 7 mm Hg
CO 5 L/min
CO 6 L/min
CO 5 L/min
CO 6 L/min
PVR 7 Wood units
PVR 4 Wood units
PVR 7 Wood units
PVR 5 Wood units
RESPONDER: TREAT WITH

CALCIUM CHANNEL BLOCKER
NON-RESPONDER: STILL
TREATABLE, BUT NOT WITH
CALCIUM CHANNEL BLOCKER
Lesson 9
First Do No HarmLearn to
Differentiate WHO Group I
PAH From Other Forms
of PH
Is It Left Heart Disease?

Symptoms
paroxysmal nocturnal
dyspnea
orthopnea
History
ECG
atrial fibrillation
absence of right axis
deviation
Echo
diabetes
left atrial enlargement
hypertension
obesity
left ventricular
hypertrophy
coronary artery disease
normal RA, RV
metabolic syndrome
abnormal diastolic filling
Problems With Incorrect Treatment

WHO Group 1 PAH: True PAH
incorrect treatment with systemic vasodilators could lead to
profound hypotension, death
WHO Group 2 PH: PH due to LHD
incorrect treatment with pulmonary vasodilators could lead to
pulmonary edema, CHF exacerbation
WHO Group 3 PH: PH due to hypoxemia/lung disease
incorrect treatment with pulmonary vasodilators could lead to
increased V/Q mismatch, worsening hypoxemia
WHO Group 4 PH: CTEPH
treating with pulmonary vasodilators likely not harmful, but
dont delay referral for potentially curative surgical
thromboendarterectomy (if indicated)
Lesson 10
Appropriate, Timely, and
Collaborative Care:
Key to Early and Effective
Treatment of PH in the
Dyspneic Patient
Goals of Collaborative Care

Clinical Practice Guidelines
Local Practitioners
PH Specialists
Best Practice
Clinical Trial Evidence
Collaborative Care With PH Centers:

Initial Steps
Local Care
Diagnostic dilemmas
Diagnostic cath/
vasodilator trial
Complex comorbidities
Failure to achieve Rx
goals
Considering prostanoids
Considering combination
Rx
Clinical trials
PH Center
Collaborative Care With PH Centers:

Ongoing Care
Local Care
Symptom evaluation
Titrate diuretics
Monitor Rx
Need to change Rx
Manage SEs
? Transplant
Evaluate acute issues
Acute hospital care
Emotional support
PH Center
Timing of Referral to a PH Center

Dependent on a local physicians level of comfort
Referral can occur at multiple junctures
Abnormal symptoms, exam, and initial screening (echo)
PH Center
Pivotal tests (without RHC)
PH Center
Diagnosis (RHC with vasodilator challenge)
PH Center
Treatment
PH Center
Treatment escalation
PH Center
Case Resolutions

Patient 1
Patient 2
Echo
Echo
LV: EF 65%
LV: EF 58%
Grade 3 diastolic
dysfunction
Grade 1 diastolic
dysfunction
RV: size
RV: size
Normal RV function
3+ RV dysfunction
PASP: 60 mm Hg
PASP: 76 mm Hg
RA: 10 mm Hg
RA: 10 mm Hg
1+ TR
2+ TR

Patient 1
Patient 2
Invasive
Hemodynamics
Invasive
Hemodynamics
RA: 15 mm Hg
RA: 12 mm Hg
mPAP: 42 mm Hg
mPAP: 41 mm Hg
PCWP: 29 mm Hg
PCWP: 10 mm Hg
CO: 6.7 L/min
CO: 2.6 L/min
PVR: 1.8 Wood units
PVR: 11.9 Wood units
BP: 172/65 mm Hg
BP: 93/69 mm Hg
Vasodilator challenge with iNO:

not indicated (high
PCWP)
Vasodilator challenge with iNO:

non-responder

Patient 1
Patient 2
Final Diagnosis
Final Diagnosis
WHO Group II
pulmonary venous
hypertension (PVH)
WHO Group I
pulmonary arterial
hypertension (PAH)
Heart failure with

preserved EF (HFpEF)
PAH due to connective

tissue disease

Patient 1: PVH
Patient 2: PAH
Clinical Course
Clinical Course
Carvedilol
Furosemide
PDE-5 inhibitor:
no improvement
Co-managed with
nephrology
ERA added
symptoms over time
Improved symptoms
Now on parenteral
prostanoid with
improved symptoms
NYHA II
NYHA II
Summary: PH Lessons
1.
PH is common, but most often due to LHD or

chronic lung disease: selective pulmonary
vasodilators are not proven in these patients
2.
PAH is rare but deadly: outcomes have

improved but not as much as we would like;
diagnosis must be made earlier
3.
Know the PH clinical clues in the dyspneic

patient
4.
Know the limitations of echo, and look beyond

PA pressure to the RV to evaluate size/function
5.
Definitive diagnosis of PH requires heart cath
Summary: PH Lessons (contd)

6.
Identify underlying cause of PH: etiology

important = prognostic and Rx implications
7.
Treatment of PH is based on correct diagnosis

and functional status
8.
Lack of response to acute vasodilator challenge

in PAH does not mean the patient is untreatable
9.
Learn to differentiate Group I PAH from other

forms of PH: when in doubt, ask for help
10. Collaborative care: key to early and effective

treatment of PH in the dyspneic patient
Thank you for your participation!

For more information on upcoming PHA
Medical Education Programs, please visit:
www.PHAssociation.org

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