Transcript SSPAH Template

Screening, Referral and Diagnosis of
Pulmonary Arterial Hypertension
TERESA DE MARCO, MD
Professor of Clinical Medicine
Director, Heart Failure and Pulmonary Hypertension Program
Medical Director, Heart Transplantation
University of California, San Francisco Medical Center
San Francisco, California
Learning Objectives (CME, CE, CPE)
● At the completion of this educational activity,
participants should be able to:
2
-
Identify patients who are at higher risk for PAH
-
Identify when a patient with suspected PAH should be
referred to a PAH-specific specialty center
Identify the common presenting symptoms for PAH
Discuss the diagnostic workup for symptoms
suggestive of PAH, and the appropriate use of various
tests
Clinical Classification of
Pulmonary Arterial Hypertension (PAH)
PAH:
Definition on Right Heart Catheterization
Increased mean pulmonary
arterial pressure (mPAP)
Normal pulmonary artery
wedge pressure (PAWP)
Increased pulmonary vascular
resistance (PVR)
Gaine SP, et al. Lancet. 1998;352:719-725.
4
>25 mm Hg at rest
or
>30 mm Hg during exercise
<15 mm Hg
>3 Wood units
Revised Clinical Classification of
Pulmonary Hypertension: 2003 Venice
● PAH
-
Idiopathic (IPAH)
Familial (FPAH)
Associated with (APAH)
•
•
•
•
•
-
Connective tissue disease
Congenital systemic-to-pulmonary shunts
Portal hypertension
HIV infection
Drugs and toxins
Other
• Thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic
telangiectasia, hemoglobinopathies, myeloproliferative disorders, splenectomy
-
Associated with significant venous or capillary involvement
• Pulmonary veno-occlusive disease (PVOD)
• Pulmonary capillary hemangiomatosis (PCH)
-
Persistent pulmonary hypertension of the newborn (PPHN)
Simonneau G, et al. J Am Coll Cardiol. 2004;43:5S-12S.
5
Revised Clinical Classification of
Pulmonary Hypertension: 2003 Venice
● Pulmonary hypertension with left heart disease
- Left-sided atrial or ventricular heart disease
- Left-sided valvular heart disease
● Pulmonary hypertension associated with lung diseases
and/or hypoxemia
- Chronic obstructive pulmonary disease
- Interstitial lung disease
- Sleep-disordered breathing
- Alveolar hypoventilation disorders
- Chronic exposure to high altitude
- Developmental abnormalities
Simonneau G, et al. J Am Coll Cardiol. 2004;43:5S-12S.
6
Revised Clinical Classification of
Pulmonary Hypertension: 2003 Venice
● Pulmonary hypertension due to chronic
thrombotic and/or embolic disease
- Thromboembolic obstruction of proximal pulmonary arteries
- Thromboembolic obstruction of distal pulmonary arteries
- Non-thrombotic pulmonary embolism
•
Tumor, parasites, foreign material
● Miscellaneous
- Sarcoidosis, histiocytosis X, lymphangiomatosis, compression
of pulmonary vessels (adenopathy, tumor, fibrosing
mediastinitis)
Simonneau G, et al. J Am Coll Cardiol. 2004;43:5S-12S.
7
Pulmonary Hypertension Connection
Registry: Etiology of PAH
Portal
Hypertension,
7.0%
Anorexigens,
3.0%
HIV, 1.0%
Congenital Heart,
11.0%
Connective
Tissue, 30.0%
n=578; female-male ratio: 77% - 33%
Calcium channel blocker use at referral: 80%
Thenappan T. Eur Respir J. 2007;30:1103-1110.
8
Idiopathic/familial,
48.0%
REVEAL Database:
Most Frequent Symptoms at Diagnosis
11%
11%
Dyspnea at rest
IPAH
APAH
13%
13.0%
Cough
14%
16.0%
Dizzy/lightheaded
20%
23.0%
Presyncope/syncope
Edema
20%
21.0%
Chest pain/discomfort
20%
23%
27%
24.0%
Other
29%
26.0%
Fatigue
83%
84.0%
Dyspnea on exertion
0
25
n=1479.
Elliott CG, et al. Chest. 2007;132(4 suppl):631S.
9
50
Incidence (%)
75
100
Survival in PAH by Etiology
1.0
0.9
Congenital
Heart Disease
Percent Survival
0.8
0.7
Portopulmonary
0.6
0.5
IPAH
0.4
Connective Tissue Disease
0.3
0.2
HIV
0.1
0
0
1
2
3
Years
IPAH, idiopathic pulmonary arterial hypertension.
McLaughlin VV, et al. Chest. 2004;126:78S-92S.
10
4
5
Screening for PAH in At-Risk
Populations
Screening for PAH Requires
High Index of Suspicion for Clinician
● Diagnosis is complex
-
IPAH and FPAH remain diagnoses of exclusion
● Early symptoms likely to be attributed to variety
of more-common conditions
● Echocardiography is most commonly used
screening tool
● Right heart cardiac catheterization required for
diagnosis
-
Best limited to centers of excellence
McGoon M, et al. Chest. 2004;126:14S-34S.
12
Alternative Diagnoses of Patients
Referred to PAH Specialty Clinic
ILD
5.0%
VTE
5.0%
Other
Structural Heart Disease
OSA
12.0%
13.0%
19%
LV Dysfunction
Obstructive Lung Disease
22.0%
24.0%
All Alternative Diagnoses
n=268, all patients referred to PAH specialty center.
Moghbelli MH, et al. Am J Respir Crit Care Med. 2008;177:A923.
13
85.0%
FPAH Genetic Screening
and Counseling
● BMPR mutations found in 70% of FPAH patients
● Penetrance is low: Only 20% of BMPR germline
mutation carriers will develop PAH
● “Second hit” theory implicates other pathways,
including serotonin transport
● At present, no guidelines exist regarding routine
genetic testing and counseling for patients with
FPAH
Humbert M. Am J Respir Crit Care Med. 2008;177:574-579.
14
Screening for PAH Associated With
Connective Tissue Disorders
● Doppler echo recommended for patients at high
risk of PAH
● DLCO recommended every 6–12 months to
improve detection of pulmonary vascular or
interstitial disease
Coghlan JG, et al. Lupus. 2006;15:138-142.
15
PAH and HIV Infection
● Sex-standardized incidence is between 68 to 138 cases
per 100,000 HIV seropositive patients PY (versus 0.16
cases per 100,000 PY in the general population)
- Females have 1.7x risk of PAH than males
- Higher prevalence among injection drug users
● AIDS diagnosis and low CD4 cell counts associated with
higher incidence of IPAH
- No apparent impact of antiretroviral therapy on IPAH occurrence
● Approximately 2/3 of patients with HIV who develop PAH
succumb to complications of PAH
Mary-Krause M. J Intern AIDS Soc. 2008;11(suppl 1):Abstract P299.
Limsukon A, et al. Mt Sinai J Med. 2006;73:1037-1044.
16
Diagnosis of PAH
PAH Diagnostic Guidelines:
Decision Analysis
Unexplained Symptoms of Dyspnea on
Exertion, Syncope/Near Syncope, Fatigue
Clinical History, Examination,
Chest X-Ray, ECG
McGoon M, et al. Chest. 2004;126:14S-34S.
18
Physical Findings Consistent With PAH
● Accentuated pulmonary component of second
heart sound (P2) at apex
-
Noted in 90% of patients with IPAH
● Early systolic ejection click
● Midsystolic ejection murmur
● Left parasternal lift
● Right ventricle S4 gallop
● Prominent jugular “a” wave
McGoon M, et al. Chest. 2004;126:14S-34S.
19
Physical Findings Consistent With PAH
● Diastolic murmur of pulmonary regurgitation
● Holosystolic murmur of tricuspid valve regurgitation
● Signs of right ventricular failure
- Right-sided third heart sound
- Jugular venous distention
- Peripheral edema, ascites
● Cool extremities
- Indicative of reduced cardiac output and peripheral
vasoconstriction
McGoon M, et al. Chest. 2004;126:14S-34S.
20
Other Physical Findings:
Differential Diagnosis/PAH Etiology
Finding
Differential Diagnosis/PAH Etiology
Cyanosis
Right-to-left shunt
Clubbing
Rare in IPAH
Congenital heart or pulmonary veno-occlusive
disease
Rales, fine rales, abnormal
breath sounds
Pulmonary congestion, parenchymal airway
disease, PVOD, PCH, etc.
Obesity, kyphoscoliosis,
enlarged tonsils
Hypoventilatory disorders
Sclerodermal skin changes,
rashes, nail-fold capillary
abnormalities
Associated connective tissue disorder
Peripheral venous
insufficiency
Venous thrombosis, pulmonary thromboembolic
disease
McGoon M, et al. Chest. 2004;126:14S-34S.
21
Screening Tests for PAH:
Electrocardiogram
● Insufficiently sensitive as a screening tool
● May indicate right-heart disease
● May provide prognostic information
McGoon M, et al. Chest. 2004;126:14S-34S.
22
Electrocardiogram Associated With
Right Ventricular Hypertrophy (RVH)
Image courtesy of Vallerie McLaughlin, MD
23
Electrocardiogram Associated With
Right Bundle Branch Block Plus RVH
Image courtesy of Vallerie McLaughlin, MD
24
Screening Tests for PAH:
Chest X-Ray Findings Consistent With PAH
● Enlarged main and hilar pulmonary artery
shadows
● “Pruning” of peripheral pulmonary vasculature
● Right ventricular enlargement
● Symptomatic patients may have normal chest xray
● Chest x-ray may reveal underlying causes of PH
McGoon M, et al. Chest. 2004;126:14S-34S.
25
Chest X-Ray Consistent With PH
Image courtesy of Vallerie McLaughlin, MD
26
MRI of Pulmonary Artery Distensibility:
Preliminary Findings
Potential Noninvasive Surrogate Marker
of Acute Vasodilator Challenge
40
mPAD (%)
30
20
10
0
Nonresponders
Responders
N = 19. P=0.01.
10% pulmonary artery distensibility predicted response to acute vasodilator challenge with
100% sensitivity and 56% specificity.
Jardim C, et al. Eur Respir J. 2007;29:476-481.
27
PAH Diagnostic Guidelines:
Decision Analysis
Clinical History, Examination,
Chest X-Ray, ECG
Is There a Reason to Suspect PH?
Yes
No
Echocardiography
Work-Up
for Other
Conditions
McGoon M, et al. Chest. 2004;126:14S-34S.
28
PAH Diagnostic Guidelines:
Decision Analysis
Echocardiography for Suspected PH
RH Analysis
CHD Analysis
LH Analysis
TRV to Estimate
RVSP, RVE, RAE, RV
Dysfunction
Abnormal Morphology,
Shunt
LV Systolic
Diastolic Dysfunction
Valvular Dysfunction
McGoon M, et al. Chest. 2004;126:14S-34S.
29
Echocardiograph:
Parasternal Long Axis
Image courtesy of Vallerie McLaughlin, MD
30
Echocardiograph:
Parasternal Short Axis
Image courtesy of Vallerie McLaughlin, MD
31
Echocardiograph:
Apical Four Chamber
Image courtesy of Vallerie McLaughlin, MD
32
Echocardiograph:
Tricuspid Regurgitation
Modified Bernoulli’s Equation:
4 x (V)² + RAP = RVSP (PASP)
V=tricuspid jet velocity (m/s); RAP= right atrial pressure; RVSP=right ventricular systolic
pressure; PASP=pulmonary artery systolic pressure.
Image courtesy of Vallerie McLaughlin, MD
33
Calculations of Estimated Pulmonary
Artery Pressures (PAP) by Doppler Echo
Measurement
Calculation
sPAP
4 x TR peak velocity2 + “RAP”
mPAP
79 – 0.45 (RVOT AT)
mPAP
4 x peak pulmonary regurgitation
velocity2
Pulmonary end
4 x (pulmonary regurgitation enddiastolic pressure diastolic velocity)2 + “RAP”
TR=tricuspid regurgitant jet velocity m/sec.
“RAP”=estimated right atrial pressure.
RVOT AT=right ventricular outflow tract acceleration time.
Bossone E, et al. Chest. 2005;127:1836-1843.
34
Limitations of Echocardiography
in Diagnosing PH
● 15% of patients will not display TR jets
-
Saline contrast can enhance TR jet
● Not all congenital heart lesions will be obvious
● Poor method to measure LH filling pressure or
cardiac output (CO)
● Small errors in TRV tracing can significantly
alter results
● TRV can underestimate RVSP or overestimate
RVSP
Stephen B, et al. Chest. 1999;116:73-77.
35
Accuracy of PH Diagnosis by
Echocardiography in Advanced Lung Disease
Diagnosis of PH
● Cohort study of lung transplant
patients (n=374)
70
● All patients
Doppler echo 24 to 48 hours
prior to RHC
● Prevalence of PH: 25%
● Echo frequently inaccurate
leading to over diagnosis of
pulmonary hypertension in
patients with advanced lung
disease
50
Studies (%)
-
60
40
30
20
10
0
Arcasoy SM, et al. Am J Respir Crit Care Med. 2003;167:735-740.
36
Overestimation
Accurate
Underestimation
No
Pulmonary
Hypertension
Pulmonary
Hypertension
Doppler Echo Overestimates PAH in Patients
With Scleroderma-Related Lung Disease
No PH
PH
100
Percent (%)
80
60
60
40
40
38
25
25
20
0
0
Overestimate PASP
Underestimate PASP
Accurate PASP
N = 13.
Chan KM. CHEST 2008; October 25-30, 2008, Philadelphia, PA. Session AP2217.
37
PAH Diagnostic Guidelines:
Further Evaluation of Patients
Echocardiography Indicates PH
Evaluate for
Associated Causes
V/Q scan
PFTs
Arterial Saturation
HIV Infection, Scleroderma,
Parenchymal Lung
Suspected
SLE, Other CTD, Liver
Chronic Pulmonary Disease, Hypoxemia,
Disease, CHD, Drugor Sleep Disorder
Emboli
Associated
McGoon M, et al. Chest. 2004;126:14S-34S.
38
Association Between Stimulant Use
and IPAH
Patients Reporting Use (n=340)
40
Patients (%)
30
28.9%
20
10
0
Idiopathic
3.8%
4.3%
PAH with Known
Risk Factors
Thromboembolic PH
Retrospective analysis at single PH center of adults with PH.
Chin KM, et al. Chest. 2006;130:1657-1663.
39
V/Q Scan for Chronic Thromboembolic
Pulmonary Hypertension (CTEPH)
● Normal V/Q scan makes CTEPH unlikely
-
Sensitivity: 90% to 100%
Specificity: 94% to 100%
● >1 segmental-sized or larger mismatched
perfusion defects seen with CTEPH
● Spiral CT may underestimate degree of
obstruction in chronic CTEPH
-
~7% false negative
McGoon M, et al. Chest. 2004;126:14S-34S.
40
Chronic Thromboembolic Pulmonary
Hypertension (CTEPH) Diagnosis
● Pulmonary angiography remains gold standard
● Signs of CTEPH
- Stenoses, complete obstructions, partial
recanalization, and intraluminal webs
● Pulmonary fiberoptic angioscopy can help
define operability in selected patients
Klepetko W, et al. J Am Coll Cardiol. 2004;43:73S-80S.
41
Pulmonary Function Testing for
PAH Suspected by Doppler Echo
● Lung volumes 60% to 80% of predicted
● Nocturnal hypoxemia occurs in >75% of patients
with IPAH
● Desaturation may increase during exercise
● DLCO <55% of predicted associated with future
development of PAH in limited systemic
sclerosis
McGoon M, et al. Chest. 2004;126:14S-34S.
Barst RJ, et al. J Am Coll Cardiol. 2004;43:40S-47S.
42
PH in Patients With
Obstructive Sleep Apnea
● Tends to be milder than PH from other causes
● Prevalence range: 17% to 53%
● Spirometric abnormalities strongly associated with PH
● PH is strongly associated with other
risk factors
- Left-sided heart disease
- Parenchymal lung disease
- Nocturnal desaturation
- Obesity
Atwood CW Jr, et al. Chest. 2004;126:72S-77S.
43
PAH Diagnostic Guidelines:
Confirmation of PAH
Echocardiography Indicates PH
Refer to PAH Specialty Center for
Right Heart Catheterization
Adapted from McGoon M, et al. Chest. 2004;126:14S-34S.
44
Right Heart Catheterization
● Required to confirm diagnosis, calculate
resistance, and guide therapy for PAH
● Excludes other etiologies for PH
-
Intracardiac or extracardiac shunts
Left-heart disease
● Measures degree of right-heart dysfunction
-
Right atrial pressure
Cardiac output
McGoon M, et al. Chest. 2004;126:14S-34S.
45
Pulmonary Artery Wedge Pressure
● Measurement is critical in PAH diagnosis
- PAH therapies increase cardiac output, therefore risk pulmonary
edema and hypoxemia in patients with left ventricular diastolic
dysfunction
● Interobserver variability in interpreting a pulmonary
artery pressure waveform is extremely large
● Physicians consistently fail to make the determination of
pulmonary wedge pressure only at end-expiration
● Direct measurement of left ventricular end-diastolic
pressure may be necessary
Ghofrani HA, et al. Circulation. 2008;118:1195-1201.
46
Hemodynamic Classification of PH
(mean PAP >25 mmHg)
Post-Capillary PH
VC
RA
RV
PA
PV
PC
Mixed
PH
Pre-capillary PH
47
LA
LV
Ao
High-Flow PH
(O2 sat run)
Hemodynamic Classification of PH
(mean PAP >25 mmHg)
Post-Capillary PH
PAWP>15 mmHg; PVR nl
VC
48
RA
RV
PA
PC
LA
PV
Ao
LV
PVP LAP LVEDP
Hemodynamic Classification of PH
(mean PAP >25 mmHg)
Post-Capillary PH
PAWP>15 mmHg; PVR nl
MR
VC
RA
RV
PA
PC
LA
PV
Ao
LV
PVP LAP LVEDP
Systemic HTN
AoV Disease
Myocardial Disease
Dilated CMP-ischemic/non-ischemic
Hypertrophic CMP
Restrictive/infiltrative CMP
Pericardial disease
49
Hemodynamic Classification of PH
(mean PAP >25 mmHg)
Post-Capillary PH
PAWP>15 mmHg; PVR nl
Atrial Myxoma
Cor Triatriatum
VC
RA
RV
PA
PC
LA
PV
PVP LAP
LV
MV Disease
50
Ao
Hemodynamic Classification of PH
(mean PAP >25 mmHg)
Post-Capillary PH
PAWP>15 mmHg; PVR nl
VC
RA
RV
PA
PC
PV
PVP
PV
compression
51
LA
LV
Ao
Hemodynamic Classification of PH
(mean PAP >25 mmHg)
PAH
Lung Diseases +/- Hypoxemia
CTEPH
{
RA
RV
PA
PV
PC
{
VC
Pre-capillary PH
PAWP < 15 mmHg;
PVR > 3 Wu
52
LA
LV
Ao
Hemodynamic Classification of PH
(mean PAP >25 mmHg)
VC
RA
RV
PA
PC
LA
PV
Ao
LV
PVP LAP LVEDP
Mixed PH
(“Reversible” vs. “Fixed”)
PAWP >15 mmHg
PVR > 3 Wu
53
Measuring Pulmonary Artery
Wedge Pressure
Pulmonary Artery Pressure Decay Curve
160
Balloon
Occlusion
Pressure (mm Hg)
140
120
ARDS
IPAH
100
80
60
40
20
0
0
2
4
6
Time (seconds)
8
10
12
Time Steady State Is Longer in IPAH Than In ARDS
ARDS: acute respiratory distress syndrome.
Souza R, et al. Crit Care. 2005;9:R132-R138.
54
Correct and Incorrect
Readings of PAWP
PA and RV Recordings
in Patient With PAH
Oudiz RJ, et al. Advances Pulm Hypertens. 2005;4:15-25.
55
PA Pressure Tracing Erroneously
Labeled As PAWP
Misclassification of PAH and PVH
Through Use of PAWP Versus LVEDP
100
90
Percent (%)
80
70
50.2
60
37.4
50
40
30
20
10
0
Misclassification of
PAH by PAWP
Misclassification of
PVH by PAWP
n=4,666, all patients undergoing LHC and RHC over 10 years at single center.
Halpern SD, et al. Am J Respir Crit Care Med. 2008;177:A259.
56
PAH and the Right Ventricle
Neurohormonal
and other
mediator activation



RV remodeling
Pulmonary hypertension

Pressure overload

Adaptive RV hypertrophy
Decreased wall stress

Maladaptive RV hypertrophy &
fibrosis
Diastolic dysfunction

RV dilation & systolic failure
RV ischemia:
]
Compensated Phase
]
Decompensating Phase
 Wall stress & heart rate
 Coronary perfusion gradient
Tricuspid regurgitation
Preload-afterload mismatch
Decreased LV compliance/preload:
Inter-ventricular septal shift
 Intrapericardial pressure
DeMarco T, et al. Adv Pulm Hypertens. 2005;4:16-26.
57
Normal CO, normal RAP
Higher RAP to maintain
adequate CO
Decompensated Phase
 CO,  RAP
 AV-DO2
Hypoxemia, acidosis,
life-threatening
dysrhythmias
Measuring Diastolic Dysfunction
Mitral Inflow
Velocity (m/s)
Normal
Diastolic
Function
DT>140 ms
0.75<E/A<2
Mild
Diastolic
Dysfunction
Moderate
Diastolic
Dysfunction
Severe
Diastolic
Dysfunction
E/A≤0.75
DT>140 ms
0.75<E/A<2
DT<140 ms
E/A>2
2.0
E
A
Doppler Tissue
Imaging of Mitral
Annular Motion
Velocity (m/s)
0
E/e’<10
0
1.5
e1
a1
E: early peak mitral inflow velocity.
A: late peak mitral inflow velocity.
DT: deceleration time of the E-wave.
e’: velocity of annulus early diastolic motion.
Bursi F, et al. JAMA. 2006;296:2209-2216.
58
E/e’<10
E/e’≥10
E/e’≥10
PAH Diagnostic Workup
Right Heart Catheterization Confirms PAH
6-Minute Walk
Borg Score
Functional
Class
Establish Baseline, Prognosis, and Document
Progression/Response to Treatment With Serial Re-Assessment
McGoon M, et al. Chest. 2004;126:14S-34S.
59
Blood Tests for Evaluation of PAH
● Antinuclear antibody (ANA)
- Up to 40% of patients with IPAH have positive but low (>1:80
dilutions) ANA titers
● Antiphospholipid antibodies
- Lupus anticoagulant, anticardiolipin antibodies
● HIV serology
● CBC with platelets
● Liver function
● Thyroid function
● Hemoglobin electrophoresis, if indicated
Barst RJ, et al. J Am Coll Cardiol. 2004;43:40S-47S.
60
NT-proBNP Elevations Correlate With
Right Ventricular Dysfunction in PH
NT-proBNP (ng/L)
5000
4000
4127
3000
2000
1000
354
0
With RVSD
N = 25.
Threshold value RVD detection: 1,685 ng/L.
Sensitivity for RVD 100%; specificity 94%.
Blyth KG, et al. Eur Respir J. 2007;29:737-744.
61
Without RVSD
BNP Predictive Value
For Adverse Outcomes
BNP (pg/mL)
644.8
Death
Cardiogenic shock
632.1
Inpatient heart failure
545.6
Outpatient heart failure
472.7
Ventricular dysfunction
424.7
WHO Class IV
470.0
WHO Class III
388.4
WHO Class II
151.7
WHO Class I
20.2
Control
12.1
N=85.
Garcia-Badillo EV. CHEST 2008; October 25-30, 2008, Philadelphia, PA. Session AP2217.
62
Distance Walked in 6 Minutes (m)
6-Minute Walk Distance Correlates
With IPAH Disease Severity
800
700
600
500
*
400
*†
300
200
*†‡
100
0
Control
NYHA II
NYHA III
*P<0.05 versus control.
†P<0.05 versus NYHA Class II.
‡P<0.05 vs NYHA Class III.
Miyamoto S, et al. Am J Respir Crit Care Med. 2000;161:487-492.
63
NYHA IV
Impact of Baseline
6-Minute Walk Distance on Survival
Epoprostenol Versus Placebo
6-Minute
Walk Distance
100
Percent Survival
80
305 + 14
Deaths
(n=8)
195 + 63
60
40
6-minute walk distance at baseline was the
only independent predictor of survival
(P<0.003)
Epoprostenol (n=41)
Conventional Therapy (n=40)
20
0
0
2
4
6
8
10
Week
Barst RJ, et al. N Engl J Med. 1996;334:296-302.
64
Survivors
(n=73)
12
Assessment of PH Severity: WHO Functional
Classification (NYHA Modification for PH)
WHO Class
Description
I
No limitation of usual activities
II
Mild limitation of usual activities
No discomfort at rest
Normal physical activity causes increased dyspnea, fatigue,
chest pain, or presyncope
III
Marked limitation of physical activity
No discomfort at rest
Less than ordinary activity causes increased dyspnea, fatigue,
chest pain, or presyncope
IV
Patient unable to perform any physical activity at rest and
may have signs of right ventricular failure
Dyspnea and/or fatigue and/or syncope/near-syncope may be
present at rest, and symptoms are increased by almost any
physical activity
Rich S. World Health Organization. 1998.
65
Prognostic Factors for Risk of
PAH Disease Progression
Lower Risk
Higher Risk
No
Yes
Progression
Gradual
Rapid
WHO Class
II, III
IV
>380 m
<325 m
Brain natriuretic peptide
<180 pg/mL
>180 pg/mL
Echo findings
Minimal RV
dysfunction
Pericardial effusion;
significant RV
dysfunction
Normal/near normal
RAP and CI
High RAP, Low CI
Evidence of RV failure
6-minute walk distance
Hemodynamics
McLaughlin VV, et al. Circulation. 2006;114:1417-1431.
66
Clinical and Hemodynamic
Predictors of Survival in PAH
NS
Concordance Index
(C statistic)
P<0.001
0.8
P<0.005
0.7
0.6
0.5
Age, Sex, WHO Class
Other Clinical Factors
ECHO & PFTs
RHC
N = 657.
Kane GC. CHEST 2008; October 25-30, 2008, Philadelphia, PA. Session AP2217.
67
Role of the Internist or Pediatrician in
Diagnosis and Management of PH
● Recognize possible PH in patient with
unexplained dyspnea on exertion
● Initiate screening
● Facilitate referral
● Provide regular local follow-up
- Assess volume status, vital signs, and oxygenation
- Monitor laboratory tests
- Manage anticoagulation with warfarin, if indicated
● Provide local emergency care
Rubin LJ, et al. Ann Intern Med. 2005;143:282-292.
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Summary:
PAH Epidemiology and Diagnosis
● PAH is rare, serious, and progressive
● PAH/PH has a wide range of etiologies
● Symptoms of PAH are nonspecific
● Screening for suspected PH can be done in local
communities
● Consider referral to specialty centers for PAH
confirmation by right heart catheterization and
initiation of PAH specific therapy
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